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Triethylamine → tert-Butyl [(1R,3S)-3-Isopropyl-3-(4-{6-methyl-4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamate

HRID 1044607
Notes
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Reaction equation

HRID 1044607 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:5]=[C:4]([C:14]([F:17])([F:16])[F:15])[CH:3]=1.[C:18]([O:22][C:23]([NH:25][C@@H:26]1[CH2:30][CH2:29][C@:28]([CH:34]([CH3:36])[CH3:35])([C:31](O)=[O:32])[CH2:27]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].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(N(CC)CC)C>C(Cl)Cl>[C:18]([O:22][C:23](=[O:24])[NH:25][C@@H:26]1[CH2:30][CH2:29][C@:28]([CH:34]([CH3:35])[CH3:36])([C:31]([N:11]2[CH2:12][CH2:13][N:8]([C:6]3[CH:5]=[C:4]([C:14]([F:17])([F:15])[F:16])[CH:3]=[C:2]([CH3:1])[N:7]=3)[CH2:9][CH2:10]2)=[O:32])[CH2:27]1)([CH3:21])([CH3:20])[CH3:19]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 598335501-[6-Methyl-4-(trifluoromethyl)pyridin-2-yl]piperazineHCID 60122293(1S,3R)-3-((Tert-butoxycarbonyl)amino)-1-isopropylcyclopentanecarboxylic acid

Product 1

HCID 59833563
tert-Butyl [(1R,3S)-3-Isopropyl-3-(4-{6-methyl-4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamate
Yield 36.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-[6-methyl-4-(trifluoromethyl)pyridin-2-yl]piperazine (280 mg, 1.1 mmol), (1S,3R)-3-[(tert-butoxycarbonyl)amino]-1-isopropylcyclopentanecarboxylic acid (460 mg, 1.7 mmol) in methylene chloride (30 mL) was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.60 g, 1.4 mmol), and triethylamine (0.20 g, 2.0 mmol). After being stirred overnight, the reaction mixture was diluted with methylene chloride, washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was purified by flash column chromatography to provide the desired product (200 mg, 35.1%). LCMS calculated for C25H37F3N4O3: (M+H) 499.3; found 499.2.

Workup

  1. washwashed with brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-49e5110e93da4a72a14afbfe6f454d59
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08563582B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes