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 1025760Notes

Reaction equation

HRID 1025760 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-8ecafa974f9b405a95301a6a5e82120c
Source dataset
uspto-grants-2014_05
Patent number
US08729063B2

Reaction notes

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