Diisopropylethylamine → 2-(bicyclo[1.1.1]pentan-1-ylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)pyrimidine-5-carbonitrile

HRID 2280753Notes

Reaction equation

[OH:1][C@H:2]1[C@H:7]([CH3:8])[CH2:6][CH2:5][C@@H:4]([NH:9][C:10]2[C:15]([C:16]#[N:17])=[CH:14][N:13]=[C:12](S(C)(=O)=O)[N:11]=2)[CH2:3]1.Cl.[C:23]12([NH2:28])[CH2:27][CH:25]([CH2:26]1)[CH2:24]2.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[C:23]12([NH:28][C:12]3[N:11]=[C:10]([NH:9][C@@H:4]4[CH2:5][CH2:6][C@@H:7]([CH3:8])[C@H:2]([OH:1])[CH2:3]4)[C:15]([C:16]#[N:17])=[CH:14][N:13]=3)[CH2:27][CH:25]([CH2:26]1)[CH2:24]2

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (446 mg, 1.437 mmol; synthesis described herein) in NMP (5 mL) was added bicyclo[1.1.1]pentan-1-amine hydrochloride (258 mg, 2.155 mmol; prepared according to Org. Lett., 13(17): 4746-4748 (2011)) and DIEA (1.255 mL, 7.18 mmol). The reaction was stirred at 80° C. for 4 h and then allowed to cool to ambient temperature. The solvent was evaporated under reduced pressure and the residue was purified by flash chromatography (0-90% ethyl acetate in hexanes) to afford 2-(bicyclo[1.1.1]pentan-1-ylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)pyrimidine-5-carbonitrile (381 mg, 1.216 mmol, 85% yield). MS (ESI): m/z 314.0 [M+1]+.

Workup

customsynthesis
temperatureto cool to ambient temperature
customThe solvent was evaporated under reduced pressure
customthe residue was purified by flash chromatography (0-90% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-5aba06f106b94c659a56cc4bdfa4c754
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139534B2

Reaction notes

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