3,3-Difluorocyclopentan-1-amine hydrochloride → HCID 58920695, compound

HRID 1365491Notes

Reaction equation

HRID 1365491 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:27][C:28](=[O:39])OC2C=CC([N+]([O-])=O)=CC=2)([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.Cl.[F:41][C:42]1([F:48])[CH2:46][CH2:45][CH:44]([NH2:47])[CH2:43]1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:27][C:28]([NH:47][CH:44]2[CH2:45][CH2:46][C:42]([F:48])([F:41])[CH2:43]2)=[O:39])([C:16]2[CH:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 534038363,3-Difluorocyclopentan-1-amine hydrochlorideHCID 66934388HCID 66934388, compound

Product 1

HCID 58920695HCID 58920695, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a crude solution of (S)-4-nitrophenyl 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethylcarbamate in DCM (1 mL) (29 mg, 0.053 mmol) was added 3,3-difluorocyclopentanamine hydrochloride (17 mg, 0.106 mmol). The reaction mixture was stirred at room temperature for 2 h and the solution turned yellow. The solution was diluted with CH2Cl2 (1 mL) and washed with 1N NaOH (3×1 mL), dried over Na2SO4, and concentrated. The yellow residue was purified by flash chromatography (4 g SiO2, 0-40% EtOAc/hexane) to furnish 1-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(3,3-difluorocyclopentyl)urea as a white solid (13 mg, 45%). LCMS: 4.06 min [M+1] 542.2 (4 min gradient, MeOH/H2O 0.1% NH4OAc) LC/MS: [M+H]=542.2 1H NMR (CDCl3, 400 MHz): 8.26 (m, 1H), 7.67 (dd, J=2 Hz, J=4 Hz, 1H), 7.52 (br, 1H), 7.38 (m, 1H), 7.22 (m, 1H), 7.18-7.08 (m, 5H), 6.57 (m, 2H), 4.50 (d, J=8 Hz, 1H), 4.46 (dd, J=4 Hz, J=8 Hz, 1H), 4.25 (m, 1H), 3.55 (d, J=12 Hz, 1H), 2.65-1.54 (m, 6H).

Workup

  1. washwashed with 1N NaOH (3×1 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe yellow residue was purified by flash chromatography (4 g SiO2, 0-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-e4e35f80eee94a3a973104f32b446b44
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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