Diisopropylethylamine → 4-(Bicyclo[1.1.1]pentan-1-ylamino)-2-(((1R,3S)-3-hydroxycyclo-hexyl)amino)pyrimidine-5-carboxamide

HRID 2280836Notes

Reaction equation

[C:1]12([NH:6][C:7]3[C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=[C:9](S(C)=O)[N:8]=3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2.C12(NC3C(C(N)=O)=CN=C(S(C)(=O)=O)N=3)CC(C1)C2.[NH2:38][C@@H:39]1[CH2:44][CH2:43][CH2:42][C@H:41]([OH:45])[CH2:40]1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[C:1]12([NH:6][C:7]3[C:12]([C:13]([NH2:15])=[O:14])=[CH:11][N:10]=[C:9]([NH:38][C@@H:39]4[CH2:44][CH2:43][CH2:42][C@H:41]([OH:45])[CH2:40]4)[N:8]=3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of 4-(bicyclo[1.1.1]pentan-1-ylamino)-2-(methylsulfinyl)pyrimidine-5-carboxamide and 4-(bicyclo[1.1.1]pentan-1-ylamino)-2-(methylsulfonyl)pyrimidine-5-carboxamide (300 mg) and (1S,3R)-3-aminocyclohexanol (152 mg, 1.32 mmol; prepared as described in Tetrahedron: Asymmetry 15:2051-2056 (2004)) in NMP (10 mL) was added DIEA (426 mg, 3.3 mmol). The resulting mixture was stirred at 100° C. overnight. The reaction mixture was purified by preparative HPLC to give the desired product (230.2 mg, 0.73 mmol, yield 66%). 1H NMR (400 MHz, CD3OD) δ ppm 8.29 (s, 1H), 3.91-3.89 (m, 1H), 3.69-3.62 (m, 1H), 2.50 (s, 1H), 2.29-2.25 (m, 1H), 2.20 (s, 6H), 1.97-1.83 (m, 3H), 1.41-1.21 (m, 4H); MS (ESI) m/z=318.2 [M+1]+.

Workup

customThe reaction mixture was purified by preparative HPLC

Sources & evidence

ORD record: ord-9703c92e52e44037b4f5370a0da416d5
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139534B2

Reaction notes

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