Diisopropylethylamine → (1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-[(1S,2S)-2-methyl-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]carbamate

HRID 1750507Notes

Reaction equation

HRID 1750507 reaction equation
Cl.[NH2:2][C:3]1([CH3:22])[CH2:7][CH2:6][CH2:5][CH:4]1[NH:8][C:9](=[O:21])[O:10][C@@H:11]1[CH2:16][C@H:15]([CH3:17])[CH2:14][CH2:13][C@H:12]1[CH:18]([CH3:20])[CH3:19].Cl[C:24]1[CH:29]=[N:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=1.CCN(C(C)C)C(C)C>CS(C)=O.O>[CH3:22][C@:3]1([NH:2][C:24]2[CH:29]=[N:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=2)[CH2:7][CH2:6][CH2:5][C@@H:4]1[NH:8][C:9](=[O:21])[O:10][C@@H:11]1[CH2:16][C@H:15]([CH3:17])[CH2:14][CH2:13][C@H:12]1[CH:18]([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 189876452-Chloro-5-(trifluoromethyl)pyrazineHCID 118308291(1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-amino-2-methylcyclopentyl)carbamate hydrochloride

Product 1

HCID 118308060(1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-[(1S,2S)-2-methyl-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]carbamate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A solution of (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl N-(2-amino-2-methylcyclopentyl)carbamate hydrochloride (5.14 g, 15.44 mmol), 2-chloro-5-(trifluoromethyl)pyrazine (CAS number 799557-87-2; 2.097 ml, 16.98 mmol) and DIPEA (8.10 ml, 46.32 mmol) in DMSO (51.5 ml) was heated to 140° C. for 17 hours. The reaction mixture was diluted with water (200 ml) and extracted with ethyl acetate (2×200 ml). The combined organics were washed with brine (3×200 ml), dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography (silica, 0-15% ethyl acetate/petrol) to afford the title compound as a single diastereomer.

Workup

  1. extractionextracted with ethyl acetate (2×200 ml)
  2. washThe combined organics were washed with brine (3×200 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (silica, 0-15% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-575c929e66c44746ae5128220d03be8e
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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