Cyclohexylamine → HCID 66576885, compound

HRID 2280735Notes

Reaction equation

[CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.Cl[C:18]1[N:23]=[C:22]([NH:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][C@H:27]([OH:31])[CH2:26]2)[C:21]([C:32]#[N:33])=[CH:20][N:19]=1>CS(C)=O>[CH:1]1([NH:7][C:18]2[N:23]=[C:22]([NH:24][C@@H:25]3[CH2:30][CH2:29][CH2:28][C@H:27]([OH:31])[CH2:26]3)[C:21]([C:32]#[N:33])=[CH:20][N:19]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of cyclohexanamine (0.181 mL, 1.583 mmol) in DMSO (5 mL), 2-chloro-4-((1R,3S)-3-hydroxycyclohexylamino)-pyrimidine-5-carbonitrile (0.200 g, 0.791 mmol; synthesis described herein) and DIEA (0.276 ml. 1.583 mmol) was heated at 70° C. overnight. After completion of reaction as indicated by LCMS and TLC the reaction mixture was allowed to cool to room temperature and concentrated. The resulting crude was purified by silica gel chromatography using a gradient of 0%-70% ethyl acetate (containing 10% ammonia saturated methanol) in hexanes. The desired product fractions were combined and concentrated to yield 2-(cyclohexylamino)-4-((1R,3S)-3-hydroxycyclohexylamino)-pyrimidine-5-carbonitrile (0.220 g, 88% yield, 98.1% pure) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.08-8.21 (m, 1H), 7.08-7.56 (m, 2H), 4.74 (d, J=3.90 Hz, 1H), 3.93-4.13 (m, 1H), 3.44-3.77 (m, 2H), 1.83-2.02 (m, 2H), 1.65-1.82 (m, 6H), 1.58 (d, J=14.84 Hz, 1H), 1.32-1.45 (m, 2H), 1.08-1.30 (m, 7H); MS (ESI) m/z 316.4 [M+1]+.

Workup

customsynthesis
customAfter completion of reaction
temperatureto cool to room temperature
concentrationconcentrated
customThe resulting crude was purified by silica gel chromatography
concentrationconcentrated

Sources & evidence

ORD record: ord-1b5c00b2299a49e794872e0adcbeeff2
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139534B2

Reaction notes

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