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

HRID 1016043
Notes
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Reaction equation

HRID 1016043 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
ParticipantsProcedureWorkupSources & evidenceReaction notes

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 AcetateSolvent
HCID 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-f09fba1193d04754a2cb2c86af4e6661
Source dataset
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07985730B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes