Water → N-[2-({(3R)-1-[4-Fluoro-4-(1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

HRID 1016053Notes

Reaction equation

HRID 1016053 reaction equation
CCN(S(F)(F)[F:7])CC.O[C:11]1([C:39]2[S:40][CH:41]=[CH:42][N:43]=2)[CH2:16][CH2:15][CH:14]([N:17]2[CH2:21][CH2:20][C@@H:19]([NH:22][C:23](=[O:38])[CH2:24][NH:25][C:26](=[O:37])[C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=3)[CH2:18]2)[CH2:13][CH2:12]1.O.CCOC(C)=O>C(Cl)Cl>[F:7][C:11]1([C:39]2[S:40][CH:41]=[CH:42][N:43]=2)[CH2:16][CH2:15][CH:14]([N:17]2[CH2:21][CH2:20][C@@H:19]([NH:22][C:23](=[O:38])[CH2:24][NH:25][C:26](=[O:37])[C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=3)[CH2:18]2)[CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 123472(Diethylamino)sulfur trifluorideHCID 58751593N-[2-({(3R)-1-[4-Hydroxy-4-(1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

Product 1

HCID 66787139N-[2-({(3R)-1-[4-Fluoro-4-(1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamideYield 33.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

DAST (0.2 mL, 1.5 mmol) was added to N-[2-({(3R)-1-[4-hydroxy-4-(1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide (0.06 g, 0.12 mmol) in CH2Cl2 (5 mL) at −78° C. with stirring under N2. The solution was allowed to warm to 0° C. slowly and stirred for 1 h. Water and EtOAc were added. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were washed with saturated NaCl, dried (MgSO4), concentrated and purified by flash chromatography and reverse-phase HPLC to give 0.020 g of the title compound in 31% yield. MS (EI) calcd: (M+H)+=499.2; found: 499.1.

Workup

  1. stirringstirred for 1 h
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with saturated NaCl
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. custompurified by flash chromatography and reverse-phase HPLC

Sources & evidence

ORD record
ord-8655938f4a5f415bb0394ffeaa4abc02
Source dataset
uspto-grants-2011_07
Patent number
US07985730B2

Reaction notes

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