4-Hydroxy-4-(2-isopropylthiazol-5-yl)cyclohexanone → N-[2-({(3R)-1-[4-Hydroxy-4-(2 isopropyl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

HRID 1025751Notes

Reaction equation

HRID 1025751 reaction equation
[OH:1][C:2]1([C:9]2[S:13][C:12]([CH:14]([CH3:16])[CH3:15])=[N:11][CH:10]=2)[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.[O:17]=[C:18]([NH:33][CH2:34][C:35](=O)[NH:36][C@@H:37]1[CH2:41]CNC1)[CH2:19][NH:20][C:21](=[O:32])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1>C(Cl)Cl.[OH-].[OH-].[Pd+2]>[OH:1][C:2]1([C:9]2[S:13][C:12]([CH:14]([CH3:16])[CH3:15])=[N:11][CH:10]=2)[CH2:7][CH2:6][CH:5]([N:36]2[CH2:37][CH2:41][C@@H:34]([NH:33][C:18](=[O:17])[CH2:19][NH:20][C:21](=[O:32])[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[CH2:35]2)[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 595561884-Hydroxy-4-(2-isopropylthiazol-5-yl)cyclohexanoneHCID 66787189N-[2-oxo-2-({2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}amino)ethyl]-3-(trifluoromethyl)benzamide

Product 1

HCID 66787069N-[2-({(3R)-1-[4-Hydroxy-4-(2 isopropyl-1,3-thiazol-5-yl)cyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamideYield 62%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a Parr hydrogenation bottle was added 4-hydroxy-4-(2-isopropyl-1,3-thiazol-5-yl)cyclohexanone (0.363 g, 1.52 mmol) and N-[2-oxo-2-({2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}amino)ethyl]-3-(trifluoromethyl)benzamide (0.435 g, 1.38 mmol), dissolved in CH2Cl2 (20 mL), followed by the addition of 10% Pd(OH)2 (0.8 g). This mixture was hydrogenated at 50 psi for 24 hour. After the catalyst was filtered and washed with methanol, the filtrate was concentrated in vacuo and chromatographed to give 0.345 g of title compound in 62% yield. MS (EI) calcd: (M+1)+=539.2; found: 539.1.

Workup

  1. filtrationAfter the catalyst was filtered
  2. washwashed with methanol
  3. concentrationthe filtrate was concentrated in vacuo
  4. customchromatographed

Sources & evidence

ORD record
ord-bf243817afed4ea1a2fc1fb30bd94c0b
Source dataset
uspto-grants-2014_05
Patent number
US08729063B2

Reaction notes

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