Triethylamine → 4-[((1R,3S)-3-Isopropyl-3-{[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclopentyl)amino]-1-(1,3-oxazol-2-yl)cyclohexanol

HRID 969565Notes

Reaction equation

HRID 969565 reaction equation
[CH:1]([C@:4]1([C:10]([N:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][C:16]([C:22]([F:25])([F:24])[F:23])=[CH:17][CH:18]=3)[CH2:13]2)=[O:11])[CH2:8][CH2:7][C@@H:6]([NH2:9])[CH2:5]1)([CH3:3])[CH3:2].[OH:26][C:27]1([C:34]2[O:35][CH:36]=[CH:37][N:38]=2)[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[CH:1]([C@:4]1([C:10]([N:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][C:16]([C:22]([F:25])([F:23])[F:24])=[CH:17][CH:18]=3)[CH2:13]2)=[O:11])[CH2:8][CH2:7][C@@H:6]([NH:9][CH:30]2[CH2:31][CH2:32][C:27]([C:34]3[O:35][CH:36]=[CH:37][N:38]=3)([OH:26])[CH2:28][CH2:29]2)[CH2:5]1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 58784490((1S,3R)-3-amino-1-isopropylcyclopentyl)(7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanoneHCID 590174384-Hydroxy-4-oxazol-2-yl-cyclohexanone

Product 1

HCID 115916914-[((1R,3S)-3-Isopropyl-3-{[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclopentyl)amino]-1-(1,3-oxazol-2-yl)cyclohexanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1R,3S)-3-isopropyl-3-{[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclopentanamine (113.0 mg, 0.3188 mmol) of Step C-2 of Example 1 in THF (1 mL) was added 4-hydroxy-4-(1,3-oxazol-2-yl)cyclohexanone (80.3 mg, 0.443 mmol) followed by triethylamine (0.5 mL, 3.6 mmol) and finally sodium triacetoxyborohydride (135 mg, 0.638 mmol). After being stirred overnight, the reaction was quenched by addition of NaOH solution. The resulting solution was extracted with methylene chloride. The extract was dried over MgSO4 and evaporated in vacuo. The residue was purified by flash chromatography eluting with EtOAc/1% NH4OH to give two isomers. Isomer 1: 73 mg. MS calculated for C28H36F3N3O3: (M+H)+520; found 520.1. Isomer 2: 56 mg. MS found 520.1.\

Workup

  1. customthe reaction was quenched by addition of NaOH solution
  2. extractionThe resulting solution was extracted with methylene chloride
  3. dry with materialThe extract was dried over MgSO4
  4. customevaporated in vacuo
  5. customThe residue was purified by flash chromatography
  6. washeluting with EtOAc/1% NH4OH
  7. customto give two isomers

Sources & evidence

ORD record
ord-a53bddcdee0642568f4b8955a5262740
Source dataset
uspto-grants-2007_12
Patent number
US07307086B2

Reaction notes

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