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 1750509Notes

Reaction equation

HRID 1750509 reaction equation
Cl[C:2]1[CH:7]=[N:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=1.Cl.[NH2:13][C:14]1([CH3:33])[CH2:18][CH2:17][CH2:16][CH:15]1[NH:19][C:20](=[O:32])[O:21][C@@H:22]1[CH2:27][C@H:26]([CH3:28])[CH2:25][CH2:24][C@H:23]1[CH:29]([CH3:31])[CH3:30].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>CS(C)=O.C(OCC)(=O)C>[CH3:33][C@:14]1([NH:13][C:2]2[CH:7]=[N:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=2)[CH2:18][CH2:17][CH2:16][C@@H:15]1[NH:19][C:20](=[O:32])[O:21][C@@H:22]1[CH2:27][C@H:26]([CH3:28])[CH2:25][CH2:24][C@H:23]1[CH:29]([CH3:30])[CH3:31]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 189876452-Chloro-5-(trifluoromethyl)pyrazineHCID 118308291(1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-amino-2-methylcyclopentyl)carbamate hydrochloride2×

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 8857Ethyl AcetateSolvent

Procedure

A solution of 2-chloro-5-(trifluoromethyl)pyrazine (CAS number 799557-87-2; 0.816 ml, 6.61 mmol), (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl N-(2-amino-2-methylcyclopentyl)carbamate hydrochloride (Intermediate 27; 2.00 g, 6.01 mmol) and DIPEA (3.15 ml, 18.02 mmol) in DMSO (10 mL) was subjected to microwave irradiation at 140° C. for 5 hours. The reaction was diluted with ethyl acetate (100 ml) and a saturated solution of sodium bicarbonate (50 m). The organics were washed with water (40 ml), brine (40 ml), dried over magnesium sulfate, filtered through a hydrophobic frit and concentrated in vacuo. The crude product was purified by column chromatography (silica, 0-20% ethyl acetate/petrol) to afford the title compound

Workup

  1. customirradiation at 140° C. for 5 hours
  2. washThe organics were washed with water (40 ml), brine (40 ml)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered through a hydrophobic frit
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography (silica, 0-20% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-e71479edfad44bf9afee6518b18ac1a0
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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