Triethylamine → Tert-butyl((1r,3s)-3-isopropyl-3-{[4-(trifluoromethyl)-3',6'-dihydro-2,4'-bipyridin-1'(2'h)-yl]carbonyl}cyclopentyl)carbamate

HRID 1261663Notes

Reaction equation

HRID 1261663 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][C@:11]([CH:17]([CH3:19])[CH3:18])([C:14]([OH:16])=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[F:22][C:23]([F:37])([F:36])[C:24]1[CH:29]=[CH:28][N:27]=[C:26]([C:30]2[CH2:31][CH2:32][NH:33][CH2:34][CH:35]=2)[CH:25]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH:17]([C@:11]1([C:14]([N:33]2[CH2:34][CH:35]=[C:30]([C:26]3[CH:25]=[C:24]([C:23]([F:37])([F:22])[F:36])[CH:29]=[CH:28][N:27]=3)[CH2:31][CH2:32]2)=[O:16])[CH2:12][CH2:13][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:10]1)([CH3:19])[CH3:18]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 60122293(1S,3R)-3-((Tert-butoxycarbonyl)amino)-1-isopropylcyclopentanecarboxylic acidHCID 685971644-(Trifluoromethyl)-1',2',3',6'-tetrahydro-2,4'-bipyridine dihydrochloride

Product 1

HCID 59833549Tert-butyl((1r,3s)-3-isopropyl-3-{[4-(trifluoromethyl)-3',6'-dihydro-2,4'-bipyridin-1'(2'h)-yl]carbonyl}cyclopentyl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1S,3R)-3-[(tert-butoxycarbonyl)amino]-1-isopropylcyclopentanecarboxylic acid (0.288 g, 1.06 mmol) and 4-(trifluoromethyl)-1′,2′,3′,6′-tetrahydro-2,4′-bipyridine dihydrochloride (0.320 g, 1.06 mmol) in dry methylene chloride (11.5 mL) was added triethylamine (0.592 mL, 4.25 mmol) followed by benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.517 g, 1.17 mmol). After being stirred at room temperature overnight, the brown reaction mixture was washed with NaHCO3 and brine, dried (MgSO4), filtered, and concentrated. The residue was purified by column chromatography on silica gel (30:70 EtOAc/hexanes) to provide a light yellow solid product: 265 mg (52%). LC-MS calculated for C25H34F3N3O3: (M+H) 482; found 382.2 (M-Boc+1).

Workup

  1. washthe brown reaction mixture was washed with NaHCO3 and brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel (30:70 EtOAc/hexanes)
  6. customto provide a light yellow solid product

Sources & evidence

ORD record
ord-7da6e1650228426eb4d3c55dd1b34650
Source dataset
uspto-grants-2013_06
Patent number
US08470827B2

Reaction notes

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