Provided is a process for preparing the compound 3 (3) or a salt or a solvate thereof, the process comprising the steps of a) Mixing the compound 4 with a mineral acid (4); b) Adding a nitrite salt or an organic nitrite derivative to the reaction mass to form a diazonium salt; c) Adding a sulfur-containing reducing agent to the reaction mass to form a hydrazyl sulfur complex, such as a hydrazyl sulfite complex; d) Hydrolysing the hydrazyl sulfur complex to provide the compound 3 or a salt or solvate thereof; and e) Optionally isolating the compound 3 or a salt or solvate thereof. Further provided is the use of the compound 3 in the synthesis of 3-[5 -Amino-4-(3-Cyanobenzoyl)-Pyrazol-1-yl]-N-Cyclopropyl-4-Methylbenzamide.

##STR00001##

The present invention discloses a hypocrellin derivative substituted both in a pen-position and in a 2-position by an amino, and a preparation method and use thereof. A general structural formula of the derivative is as represented by formulas I-a to I-d: ##STR00001## The hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino prepared in the present invention has a maximum absorption wavelength of 600-650 nm and a molar extinction coefficient reaching about 20000-40000 M.sup.−1cm.sup.−1. Compared with unmodified hypocrellin or hypocrellin having only a 2-position modified, an absorption spectrum of the derivative is significantly red-shifted and the molar extinction coefficient is greatly improved, and the derivative can efficiently produce reactive oxygen species such as singlet oxygen in a photosensitive condition. In the same condition, the hypocrellin derivative substituted both in a pen-position and in a 2-position by an amino involved in the present invention, when used as a photosensitizer, has a stronger ability to photo-dynamically inactivate tumor cells than the first and second generation commercial photosensitizers.

The present invention discloses a hypocrellin derivative substituted both in a pen-position and in a 2-position by an amino, and a preparation method and use thereof. A general structural formula of the derivative is as represented by formulas I-a to I-d: ##STR00001## The hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino prepared in the present invention has a maximum absorption wavelength of 600-650 nm and a molar extinction coefficient reaching about 20000-40000 M.sup.−1cm.sup.−1. Compared with unmodified hypocrellin or hypocrellin having only a 2-position modified, an absorption spectrum of the derivative is significantly red-shifted and the molar extinction coefficient is greatly improved, and the derivative can efficiently produce reactive oxygen species such as singlet oxygen in a photosensitive condition. In the same condition, the hypocrellin derivative substituted both in a pen-position and in a 2-position by an amino involved in the present invention, when used as a photosensitizer, has a stronger ability to photo-dynamically inactivate tumor cells than the first and second generation commercial photosensitizers.

The present invention provided a continuous flow process for the synthesis of phenylhydrazine salts and substituted phenylhydrazine salts. Diazotization, reduction, acidic hydrolysis and salifying with acids are innovatively integrated together. Using acidic liquids of aniline or substituted aniline, diazotization reagents, reductants and acids as raw materials, phenylhydrazine derivative salts is obtained through the synthesis process, which is a three-step continuous tandem reaction including diazotization, reduction, acidic hydrolysis and salifying. The described synthesis process is a kind of integrated solutions, which is carried out in an integrated reactor. The feed inlets of the integrated reactor are continuously filled with raw materials. In the integrated reactor, diazotization, reduction, acidic hydrolysis and salifying are carried out continuously and orderly, and phenylhydrazine salts or substituted phenylhydrazine salts is obtained in the outlet of the integrated reactor without interruption. The total reaction time is no more than 20 min.

The present invention provided a continuous flow process for the synthesis of phenylhydrazine salts and substituted phenylhydrazine salts. Diazotization, reduction, acidic hydrolysis and salifying with acids are innovatively integrated together. Using acidic liquids of aniline or substituted aniline, diazotization reagents, reductants and acids as raw materials, phenylhydrazine derivative salts is obtained through the synthesis process, which is a three-step continuous tandem reaction including diazotization, reduction, acidic hydrolysis and salifying. The described synthesis process is a kind of integrated solutions, which is carried out in an integrated reactor. The feed inlets of the integrated reactor are continuously filled with raw materials. In the integrated reactor, diazotization, reduction, acidic hydrolysis and salifying are carried out continuously and orderly, and phenylhydrazine salts or substituted phenylhydrazine salts is obtained in the outlet of the integrated reactor without interruption. The total reaction time is no more than 20 min.

The present invention provided a continuous flow process for the synthesis of phenylhydrazine salts and substituted phenylhydrazine salts. Diazotization, reduction, acidic hydrolysis and salifying with acids are innovatively integrated together. Using acidic liquids of aniline or substituted aniline, diazotization reagents, reductants and acids as raw materials, phenylhydrazine derivative salts is obtained through the synthesis process, which is a three-step continuous tandem reaction including diazotization, reduction, acidic hydrolysis and salifying. The described synthesis process is a kind of integrated solutions, which is carried out in an integrated reactor. The feed inlets of the integrated reactor are continuously filled with raw materials. In the integrated reactor, diazotization, reduction, acidic hydrolysis and salifying are carried out continuously and orderly, and phenylhydrazine salts or substituted phenylhydrazine salts is obtained in the outlet of the integrated reactor without interruption. The total reaction time is no more than 20 min.

A quaternary ammonium salt of formula (I): wherein X is a linking group; Y is O, NH or NR.sup.1 wherein R.sup.1 is H or an optionally substituted hydrocarbyl group; Q.sup.+ is a moiety that includes a quaternary ammonium cation; A.sup.− is an anion; R.sup.2 is an optionally substituted alkylene group; R.sup.3 is hydrogen or an optionally substituted hydrocarbyl group; and n is 0 or a positive integer; provided that n is not 0 when R.sup.3 is hydrogen. ##STR00001##

A quaternary ammonium salt of formula (I): wherein X is a linking group; Y is O, NH or NR.sup.1 wherein R.sup.1 is H or an optionally substituted hydrocarbyl group; Q.sup.+ is a moiety that includes a quaternary ammonium cation; A.sup.− is an anion; R.sup.2 is an optionally substituted alkylene group; R.sup.3 is hydrogen or an optionally substituted hydrocarbyl group; and n is 0 or a positive integer; provided that n is not 0 when R.sup.3 is hydrogen. ##STR00001##

The present invention discloses a hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino, and a preparation method and use thereof. A general structural formula of the derivative is as represented by formulas I-a to I-d:

##STR00001##

The hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino prepared in the present invention has a maximum absorption wavelength of 600-650 nm and a molar extinction coefficient reaching about 20000-40000 M.sup.−1cm.sup.−1. Compared with unmodified hypocrellin or hypocrellin having only a 2-position modified, an absorption spectrum of the derivative is significantly red-shifted and the molar extinction coefficient is greatly improved, and the derivative can efficiently produce reactive oxygen species such as singlet oxygen in a photosensitive condition. In the same condition, the hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino involved in the present invention, when used as a photosensitizer, has a stronger ability to photo-dynamically inactivate tumor cells than the first and second generation commercial photosensitizers.

The present invention discloses a hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino, and a preparation method and use thereof. A general structural formula of the derivative is as represented by formulas I-a to I-d:

##STR00001##

The hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino prepared in the present invention has a maximum absorption wavelength of 600-650 nm and a molar extinction coefficient reaching about 20000-40000 M.sup.−1cm.sup.−1. Compared with unmodified hypocrellin or hypocrellin having only a 2-position modified, an absorption spectrum of the derivative is significantly red-shifted and the molar extinction coefficient is greatly improved, and the derivative can efficiently produce reactive oxygen species such as singlet oxygen in a photosensitive condition. In the same condition, the hypocrellin derivative substituted both in a peri-position and in a 2-position by an amino involved in the present invention, when used as a photosensitizer, has a stronger ability to photo-dynamically inactivate tumor cells than the first and second generation commercial photosensitizers.