Diisopropylethylamine → (1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-{[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]amino}-2-methylcyclopentyl)carbamate

HRID 1750516Notes

Reaction equation

HRID 1750516 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].F[C:24]1[C:29]([F:30])=[CH:28][C:27]([C:31]([F:34])([F:33])[F:32])=[CH:26][N:25]=1.CCN(C(C)C)C(C)C>CS(C)=O>[F:30][C:29]1[C:24]([NH:2][C:3]2([CH3:22])[CH2:7][CH2:6][CH2:5][CH:4]2[NH:8][C:9](=[O:21])[O:10][C@@H:11]2[CH2:16][C@H:15]([CH3:17])[CH2:14][CH2:13][C@H:12]2[CH:18]([CH3:19])[CH3:20])=[N:25][CH:26]=[C:27]([C:31]([F:33])([F:32])[F:34])[CH:28]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 134215472,3-Difluoro-5-(trifluoromethyl)pyridineHCID 118308291(1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-amino-2-methylcyclopentyl)carbamate hydrochloride2×

Product 1

HCID 118308092(1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-{[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]amino}-2-methylcyclopentyl)carbamate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl N-(2-amino-2-methylcyclopentyl)carbamate hydrochloride (Intermediate 27; 1.00 g, 3.00 mmol), 2,3-difluoro-5-(trifluoromethyl)pyridine (CAS number 89402-42-6; 0.412 ml, 3.30 mmol) and DIPEA (1.57 ml, 9.01 mmol) in DMSO (10 ml) was subjected to microwave irradiation at 140° C. for 3 hours. The reaction was then partitioned between ethyl acetate (10 ml) and water (10 ml), filtered through a hydrophobic frit and concentrated in vacuo. The residue was purified by column chromatography (silica, 0-12% diethyl ether/petrol) to afford the title compound as a single trans-enantiomer.

Workup

  1. customirradiation at 140° C. for 3 hours
  2. customThe reaction was then partitioned between ethyl acetate (10 ml) and water (10 ml)
  3. filtrationfiltered through a hydrophobic frit
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (silica, 0-12% diethyl ether/petrol)

Sources & evidence

ORD record
ord-5dd3c7a7a1de4284a6fc38991e80f594
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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