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

HRID 1750569Notes

Reaction equation

HRID 1750569 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[N:29]=[CH: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>[CH3:22][C:3]1([NH:2][C:24]2[N:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=2)[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]([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 133170192-Chloro-5-(trifluoromethyl)pyrimidineHCID 118308291(1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-amino-2-methylcyclopentyl)carbamate hydrochloride2×

Product 1

HCID 118308223(1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl N-(2-methyl-2-{[5-(trifluoromethyl)pyrimidin-2-yl]amino}cyclopentyl)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; 2.0 g, 6.01 mmol), 2-chloro-5-(trifluoromethyl)pyrimidine (CAS number 69034-12-4; 1.21 g, 6.61 mmol) and DIPEA (3.15 ml, 18.02 mmol) in dry DMSO (15 ml) was subjected to microwave irradiation at 140° C. for 4 hours. The reaction was partitioned between ethyl acetate and brine. The aqueous layer was extracted further with ethyl acetate (2×100 ml). The combined organics were washed with brine (3×125 ml), dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica, 0-30% diethyl ether/petrol) to afford the title compound as a single trans-enantiomer.

Workup

  1. customirradiation at 140° C. for 4 hours
  2. customThe reaction was partitioned between ethyl acetate and brine
  3. extractionThe aqueous layer was extracted further with ethyl acetate (2×100 ml)
  4. washThe combined organics were washed with brine (3×125 ml)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (silica, 0-30% diethyl ether/petrol)

Sources & evidence

ORD record
ord-f6bf450ddb074afb8b54154968dfa2f6
Source dataset
uspto-grants-2015_10
Patent number
US09156829B2

Reaction notes

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