Triethylamine → n-{(3r)-1-[4-Hydroxy-4-(2-isopropyl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl}-4-oxo-4-[3-(trifluoromethyl)phenyl]butanamide

HRID 1173258Notes

Reaction equation

HRID 1173258 reaction equation
Cl.Cl.Cl.[NH2:4][C@@H:5]1[CH2:9][CH2:8][N:7]([CH:10]2[CH2:15][CH2:14][C:13]([C:17]3[S:21][C:20]([CH:22]([CH3:24])[CH3:23])=[N:19][CH:18]=3)([OH:16])[CH2:12][CH2:11]2)[CH2:6]1.[O:25]=[C:26]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=1)[CH2:27][CH2:28][C:29](O)=[O:30].CCN(CC)CC.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C.CCOC(C)=O>[OH:16][C:13]1([C:17]2[S:21][C:20]([CH:22]([CH3:24])[CH3:23])=[N:19][CH:18]=2)[CH2:12][CH2:11][CH:10]([N:7]2[CH2:8][CH2:9][C@@H:5]([NH:4][C:29](=[O:30])[CH2:28][CH2:27][C:26](=[O:25])[C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:39])[F:40])[CH:33]=3)[CH2:6]2)[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 134088364-Oxo-4-(3-trifluoromethylphenyl)butyric acidHCID 667872284-[(3R)-3-aminopyrrolidin-1-yl]-1-(2-isopropyl-1,3-thiazol-5-yl)cyclohexanol 3HCl salt

Product 1

HCID 58751615n-{(3r)-1-[4-Hydroxy-4-(2-isopropyl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl}-4-oxo-4-[3-(trifluoromethyl)phenyl]butanamideYield 25%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4[(3R)-3-aminopyrrolidin-1-yl]-1-(2-isopropyl-1,3-thiazol-5-yl)cyclohexanol 3HCl salt (0.233 g, 0.557 mmol) and 4-oxo-4-[3-(trifluoromethyl)phenyl]butanoic acid (0.15 g, 0.61 mmol) in DMF (5 mL) was added Et3N (0.34 mL, 2.44 mmol) followed by BOP (0.296 g, 0.67 mmol). The mixture was stirred overnight at room temperature. Then the reaction mixture was diluted with EtOAc and washed with saturated Na2CO3 and brine. The organic layer was dried (MgSO4), concentrated and flash chromatographed (EtOAc to 10% MeOH/EtOAc) to give 0.075 g of the title compound. MS (EI) calculated: MS (EI) calcd: (M+H)+=538.2; found: 538.1.

Workup

  1. washwashed with saturated Na2CO3 and brine
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated
  4. customflash chromatographed (EtOAc to 10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-60c79aa9162d494d951c7a8837a2cb86
Source dataset
uspto-grants-2010_11
Patent number
US07834021B2

Reaction notes

Loading…