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

HRID 1436802Notes

Reaction equation

HRID 1436802 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 sulotion of 1-[6-methyl-4-(trifluoromethyl)pyridin-2-yl]piperazine (280 mg, 1.1 mmol), (1 S ,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-447a9714401a4ef1b97ba0348ea6c0f2
Source dataset
uspto-grants-2009_11
Patent number
US07618970B2

Reaction notes

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