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

HRID 1261678Notes

Reaction equation

HRID 1261678 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>[CH:34]([C@:28]1([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])[CH2:29][CH2:30][C@@H:26]([NH:25][C:23](=[O:24])[O:22][C:18]([CH3:20])([CH3:19])[CH3:21])[CH2:27]1)([CH3:36])[CH3:35]

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 59833563tert-Butyl [(1R,3S)-3-Isopropyl-3-(4-{6-methyl-4-(trifluoromethyl)pyridin-2-yl]piperazin-1-ylcarbonyl)cyclopentyl]carbamateYield 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+1) 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-4906b762b6b64244b2aa221eb9cd057e
Source dataset
uspto-grants-2013_06
Patent number
US08470827B2

Reaction notes

Loading…