2-Chlorocyclohexanone → HCID 58897199, compound

HRID 1993610Notes

Reaction equation

HRID 1993610 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@:8]([C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([F:28])[CH:19]=2)([NH:14][C:15]([NH2:17])=[S:16])[CH2:9][C:10]([O:12][CH3:13])=[O:11])=[N:6][CH:7]=1.Cl[CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][C:31]1=O>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@:8]([C:18]2[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[C:20]([F:28])[CH:19]=2)([NH:14][C:15]2[S:16][C:30]3[CH2:35][CH2:34][CH2:33][CH2:32][C:31]=3[N:17]=2)[CH2:9][C:10]([O:12][CH3:13])=[O:11])=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 132032-ChlorocyclohexanoneHCID 58897187HCID 58897187, compound

Product 1

HCID 58897199HCID 58897199, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (S)-methyl 3-(5-chloropyridin-2-yl)-3-(3-fluoro-5-(trifluoromethyl)phenyl)-3-thioureidopropanoate (100 mg, 0.23 mmol) and 2-chloro cyclohexanone (36 mg, 0.28 mmol) in MeOH (5.0 mL) was heated at 70° C. for 18 h. The concentrated reaction mixture was purified by silica gel ISCO chromatography (12 g column) using hexanes/EtOAc (0-30% over 15 min). (S)-methyl 3-(5-chloropyridin-2-yl)-3-(3-fluoro-5-(trifluoromethyl)phenyl)-3-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-ylamino)propanoate was isolated as a clear oil, (13 mg, 11% yield). LCMS: 1.70 min [M+1] 514.3 (2 min gradient, MeOH/H2O 0.1% TFA); HPLC: 3.65 min (4 min gradient, MeOH/H2O 0.2% PPA); Purity 96%; NMR: 400 MHz 1H (CDCl3) 8.43 ppm, 1H, d, J=2.20 Hz; 7.55 ppm, 1H, dd, J=8.57, 2.42 Hz; 7.49 ppm, 1H, s; 7.29 ppm, 2H, m; 7.14 ppm, 1H, d, J=7.91 Hz; 3.98 ppm, 1H, d, J=15.82 Hz; 3.70 ppm, 1H, d, J=15.82 Hz; 3.60 ppm, 1H, s; 3.47 ppm, 3H, s; 2.40 ppm, 4H, m; 1.68 ppm, 4H, m.

Workup

  1. customThe concentrated reaction mixture
  2. customwas purified by silica gel ISCO chromatography (12 g column)
  3. customhexanes/EtOAc (0-30% over 15 min)

Sources & evidence

ORD record
ord-eae285fd916f4792be44923632ca082f
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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