Triethylamine → N-[2-[(3S)-3-[[4-hydroxy-4-(5-pyrimidin-2-ylpyridin-2-yl)cyclohexyl]amino]pyrrolidin-1-yl]-2-oxoethyl]-3-(trifluoromethyl)benzamide

HRID 2367016Notes

Reaction equation

HRID 2367016 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:7][CH2:6][N:5]([C:8](=[O:23])[CH2:9][NH:10][C:11](=[O:22])[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[CH2:4]1.[OH:24][C:25]1([C:32]2[CH:37]=[CH:36][C:35]([C:38]3[N:43]=[CH:42][CH:41]=[CH:40][N:39]=3)=[CH:34][N:33]=2)[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)C(C)C>[OH:24][C:25]1([C:32]2[CH:37]=[CH:36][C:35]([C:38]3[N:39]=[CH:40][CH:41]=[CH:42][N:43]=3)=[CH:34][N:33]=2)[CH2:30][CH2:29][CH:28]([NH:2][C@H:3]2[CH2:7][CH2:6][N:5]([C:8](=[O:23])[CH2:9][NH:10][C:11](=[O:22])[C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=3)[CH2:4]2)[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 578033584-Hydroxy-4-[5-(2-pyrimidinyl)-2-pyridyl]cyclohexanoneHCID 69003059(S)-N-(2-(3-aminopyrrolidin-1-yl)-2-oxoethyl)-3-(trifluoromethyl)benzamide hydrochloride

Product 1

HCID 11192346N-[2-[(3S)-3-[[4-hydroxy-4-(5-pyrimidin-2-ylpyridin-2-yl)cyclohexyl]amino]pyrrolidin-1-yl]-2-oxoethyl]-3-(trifluoromethyl)benzamideYield 66.4%

Reagents, catalysts & solvents 1

HCID 6560IsobutanolSolvent

Procedure

To a solution of N-{2-[(3S)-3-aminopyrrolidin-1-yl]-2-oxoethyl}-3-(trifluoromethyl)benzamide hydrochloride (22.10 g, 47.1 mmol) and 4-hydroxy-4-(5-pyrimidin-2-ylpyridin-2-yl)cyclohexanone (12.7 g, 47.1 mmol) in isobutyl alcohol (80.0 mL) was added triethylamine (19.7 mL, 141 mmol). The reaction mixture was cooled in an ice bath and stirred for 30 minutes. To it was added sodium triacetoxyborohydride (11.0 g, 51.8 mmol) in portion. After being stirred at room temperature for 4 hours, the solvent was removed by evaporation under reduced pressure. Saturated aqueous NaHCO3 solution was added and the solution was extracted with ethyl acetate (150×3). The combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was columned on silica gel, eluting with ethyl acetate (1% NH4OH aqueous solution)/methanol (95/5 to 80/20). The appropriate fractions were combined and concentrated to give the title compound as a white powder (17.77 g). MS (M+H) 569.

Workup

  1. temperatureThe reaction mixture was cooled in an ice bath
  2. stirringAfter being stirred at room temperature for 4 hours
  3. customthe solvent was removed by evaporation under reduced pressure
  4. additionSaturated aqueous NaHCO3 solution was added
  5. extractionthe solution was extracted with ethyl acetate (150×3)
  6. washThe combined extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washeluting with ethyl acetate (1% NH4OH aqueous solution)/methanol (95/5 to 80/20)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c125e9f334bd4917a705405845f19a22
Source dataset
uspto-grants-2014_04
Patent number
US08697870B2

Reaction notes

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