Diisopropylethylamine → HCID 86676340, compound

HRID 2280733Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]#[N:10])=[CH:4][N:3]=1.[NH2:11][C@H:12]1[CH2:17][CH2:16][CH2:15][C@@H:14]([OH:18])[CH2:13]1.CCN(C(C)C)C(C)C>C(O)C>[Cl:8][C:6]1[C:5]([C:9]#[N:10])=[CH:4][N:3]=[C:2]([NH:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][C@H:14]([OH:18])[CH2:13]2)[N:7]=1.[Cl:1][C:2]1[N:7]=[C:6]([NH:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][C@H:14]([OH:18])[CH2:13]2)[C:5]([C:9]#[N:10])=[CH:4][N:3]=1

Participants

Conditions

Temperature: -60 °C

Procedure

2,4-Dichloropyrimidine-5-carbonitrile (900 mg, 5.17 mmol) in anhydrous ethanol (5 mL) and (1R,3S)-3-amino-cyclohexanol (624 mg, 5.43 mmol; prepared as described in Tetrahedron: Asymmetry 15 (2004) 2051-2056) in anhydrous ethanol (5 mL) were mixed at −60° C. and then DIEA (1.0 g, 7.75 mmol) was added dropwise. The mixture was stirred at −60° C. for 1 h and then at room temperature overnight. Volatile fractions were removed and the residue was purified on silica gel (eluting with 9.1%-33% ethyl acetate in petroleum ether) to give 4-chloro-2-((1R,3S)-3-hydroxycyclohexylamino)-pyrimidine-5-carbonitrile (600 mg, 2.38 mmol, yield 46%) as a white solid and 2-chloro-4-((1R,3S)-3-hydroxycyclohexylamino)pyrimidine-5-carbonitrile (270 mg, 1.07 mmol, yield 20%; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.55 (s, 1H), 8.46 (d, J=7.81 Hz, 1H), 4.83 (d, J=3.90 Hz, 1H), 3.95-4.11 (m, 1H), 3.45-3.61 (m, 1H), 1.93 (d, J=11.71 Hz, 1H), 1.60-1.84 (m, 3H), 1.03-1.50 (m, 4H); MS (ESI) m/z. 253.2 [M+1]+) as a white solid. The regiochemistry of the minor regioisomer was confirmed in step B below.

Workup

customat room temperature
customovernight
customVolatile fractions were removed
customthe residue was purified on silica gel (eluting with 9.1%-33% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-35479928f96846149554b9386e6126a8
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139534B2

Reaction notes

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