Sodium triacetoxyborohydride → N-[2-Oxo-2-({(3R)-1-[4-(1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl}amino)ethyl]-3-(trifluoromethyl)benzamide

HRID 1025755Notes

Reaction equation

HRID 1025755 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:6]1[CH2:11][CH2:10][C:9](=O)[CH2:8][CH2:7]1.[O:13]=[C:14]([NH:29][CH2:30][C:31](=O)[NH:32][C@@H:33]1[CH2:37]CNC1)[CH2:15][NH:16][C:17](=[O:28])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CC(O)=O.C(Cl)Cl.CCOC(C)=O>[O:13]=[C:14]([NH:29][C@@H:30]1[CH2:37][CH2:33][N:32]([CH:9]2[CH2:10][CH2:11][CH:6]([C:2]3[S:1][CH:5]=[CH:4][N:3]=3)[CH2:7][CH2:8]2)[CH2:31]1)[CH2:15][NH:16][C:17](=[O:28])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=1

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 595561194-(Thiazol-2-yl)cyclohexan-1-oneHCID 66787189N-[2-oxo-2-({2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}amino)ethyl]-3-(trifluoromethyl)benzamide

Product 1

HCID 58751589N-[2-Oxo-2-({(3R)-1-[4-(1,3-thiazol-2-yl)cyclohexyl]pyrrolidin-3-yl}amino)ethyl]-3-(trifluoromethyl)benzamideYield 85%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21922555Acetic acid methylene chlorideSolvent

Procedure

To a mixture of 4-(1,3-thiazol-2-yl)cyclohexanone (0.069 g, 0.38 mmol) and N-[2-oxo-2-({2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}amino)ethyl]-3-(trifluoromethyl)benzamide (0.10 g, 0.32 mmol) in 2% AcOH/CH2Cl2 (10 mL) was added NaB(OAc)3H (0.134 g, 0.634 mmol). After being stirred overnight at room temperature under N2, the reaction mixture was diluted with EtOAc and washed with saturated Na2CO3. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried (MgSO4), concentrated and flash chromatographed [EtOAc to MeOH/EtOAc (1:9) then to 5% MeOH/EtOAc/Et3N (1:9:0.5)] to give 0.129 g of the title compound in 85% yield. MS (EI) calcd: (M+H)+=480.2; found: 480.3.

Workup

  1. washwashed with saturated Na2CO3
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated
  5. customflash chromatographed [EtOAc to MeOH/EtOAc (1:9)

Sources & evidence

ORD record
ord-2d4af562569846e89ff2dbb617bcef7c
Source dataset
uspto-grants-2014_05
Patent number
US08729063B2

Reaction notes

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