Water → Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

HRID 711460Notes

Reaction equation

Cl[C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)[N:3]=1.[NH2:20][C@@H:21]1[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]1[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31].O.CCOC(C)=O>CC(N(C)C)=O>[C:30]([O:29][C:28]([NH:27][C@H:22]1[CH2:23][CH2:24][CH2:25][CH2:26][C@H:21]1[NH:20][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)[N:3]=1)=[O:34])([CH3:33])([CH3:31])[CH3:32]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of methyl 6-chloro-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate (155 mg, 0.560 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (144 mg, 0.672 mmol) in DMA (2 mL) was stirred at 150° C. for 1 h under microwave irradiation. To the resulting mixture were added H2O and EtOAc. The organic phase was washed with H2O (3×) and brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2 to give the title compound as a yellow oil (100 mg, 39.3%). 1H NMR (500 MHz, CDCl3) δ ppm 1.34-1.95 (m, 17H), 3.92 (s, 3H), 3.93 (s, 3H), 4.87 (br s, 1H), 5.66 (br s, 1H), 6.52 (s, 1H), 7.78-7.83 (m, 2H). [M+H] calc'd for C23H30N6O4, 455. found, 455.

Workup

washThe organic phase was washed with H2O (3×) and brine
dry with materialdried over MgSO4
customevaporated
customThe residue was purified by chromatography on SiO2

Sources & evidence

ORD record: ord-267bfe047da5480290ae75cd08e56914
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181255B2

Reaction notes

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