Cyclohexylamine → 2-[2-(4-Chloro-phenyl)-2H-indazol-3-yl]-2,N-dicyclohexyl-acetamide

HRID 1678620Notes

Reaction equation

HRID 1678620 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]([OH:20])=O)=[C:15]3[C:10]([CH:11]=[CH:12][CH:13]=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1.[CH:27]1([NH2:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[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]([NH:33][CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[O:20])=[C:15]3[C:10]([CH:11]=[CH:12][CH:13]=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 7965CyclohexylamineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 67131005[2-(4-Chloro-phenyl)-2H-indazol-3-yl]-cyclohexyl-acetic acid

Product 1

HCID 451103842-[2-(4-Chloro-phenyl)-2H-indazol-3-yl]-2,N-dicyclohexyl-acetamideYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cold solution of [2-(4-chloro-phenyl)-2H-indazol-3-yl]-cyclohexyl-acetic acid (9 mg, 24 μmol and cyclohexylamine (2.3 μl, 24 μmol; CAS Reg. No. 108-91-8) in CH2Cl2 (1 ml) under an argon atmosphere was added bromotripyrrolidinophosphonium hexafluorophosphate (17 mg, 36 umol) and N,N-diisopropylethylamine (10 ul, 72 umol). The reaction mixture was stirred for 5 d at ambient temperature, poured onto ice water/1 N aqueous NaOH solution 1/1 and extracted two times with iPrOAc. The combined extracts were washed with ice water/1 N aqueous HCl solution 1/1 and brine and dried over Na2SO4. After filtration the solvent was removed under reduced pressure and the residue was purified by preparative thin layer chromatography (silica gel, iPrOAc/heptane) to give the title compound (5 mg, 11 μmol; 46%) as colorless foam. MS: m/e=450.3 [M+H+].

Workup

  1. additionpoured onto ice water/1 N aqueous NaOH solution 1/1
  2. extractionextracted two times with iPrOAc
  3. washThe combined extracts were washed with ice water/1 N aqueous HCl solution 1/1 and brine
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration the solvent
  6. customwas removed under reduced pressure
  7. customthe residue was purified by preparative thin layer chromatography (silica gel, iPrOAc/heptane)

Sources & evidence

ORD record
ord-e645341f91f84e568a94158b4a3fdf23
Source dataset
uspto-grants-2011_08
Patent number
US08008505B2

Reaction notes

Loading…