Pyridine → 4-{2-[2-(4-Chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-2-cyclohexyl-2-hydroxy-acetylamino}-3-fluoro-benzoic acid ethyl ester

HRID 1678622Notes

Reaction equation

HRID 1678622 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([CH:17]([CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[C:18](O)=[O:19])=[C:15]3[C:10]([CH2:11][CH2:12][CH2:13][CH2:14]3)=[N:9]2)=[CH:4][CH:3]=1.N1C=CC=CC=1.S(Cl)(Cl)=[O:34].[CH2:37]([O:39][C:40](=[O:49])[C:41]1[CH:46]=[CH:45][C:44]([NH2:47])=[C:43]([F:48])[CH:42]=1)[CH3:38]>C(Cl)Cl>[CH2:37]([O:39][C:40](=[O:49])[C:41]1[CH:46]=[CH:45][C:44]([NH:47][C:18](=[O:19])[C:17]([C:16]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:9]=[C:10]3[C:15]=2[CH2:14][CH2:13][CH2:12][CH2:11]3)([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[OH:34])=[C:43]([F:48])[CH:42]=1)[CH3:38]

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 24386Thionyl ChlorideHCID 20536493Ethyl 4-amino-3-fluorobenzoateHCID 67131112[2-(4-Chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-cyclohexyl-acetic acid

Product 1

HCID 671309474-{2-[2-(4-Chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-2-cyclohexyl-2-hydroxy-acetylamino}-3-fluoro-benzoic acid ethyl esterYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [2-(4-chloro-phenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-cyclohexyl-acetic acid (60 mg, 161 μmol) in CH2Cl2 (0.8 ml) under an argon atmosphere was added pyridine (16 μl, 202 μmol) and thionyl chloride (14 μl, 193 μmol). 4-Amino-3-fluoro-benzoic acid ethyl ester (29 mg, 161 μmol; CAS Reg. No. 73792-12-8) and pyridine (16 μl, 202 μmol) were added and the reaction mixture was stirred at ambient temperature for 48 h. Ice water/25% aqueous HCl solution 1/1 was added and the mixture was extracted three times with CH2Cl2. The combined extracts were washed with ice water/brine 1/1 and dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a brown solid which was purified by preparative thick layer chromatography (silica gel, iPrOAc/heptane) to obtain the title compound (9 mg, 16 μmol; 10%) as colorless solid. MS: m/e=554.4 [M+H+].

Workup

  1. extractionthe mixture was extracted three times with CH2Cl2
  2. washThe combined extracts were washed with ice water/brine 1/1
  3. dry with materialdried over Na2SO4
  4. filtrationAfter filtration the solvent
  5. customwas removed under reduced pressure
  6. customto give a brown solid which
  7. customwas purified by preparative thick layer chromatography (silica gel, iPrOAc/heptane)

Sources & evidence

ORD record
ord-9cefb767661c43b8aa74ed859ba49de6
Source dataset
uspto-grants-2011_08
Patent number
US08008505B2

Reaction notes

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