Diisopropylethylamine → 4-((1R,3S)-3-Hydroxycyclohexylamino)-2-(4-methoxy-bicyclo[2.2.2]octan-1-ylamino)pyrimidine-5-carboxamide

HRID 2280831Notes

Reaction equation

[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9]2[C:14]([C:15]([NH2:17])=[O:16])=[CH:13][N:12]=[C:11](S(C)(=O)=O)[N:10]=2)[CH2:3]1.Cl.[CH3:23][O:24][C:25]12[CH2:32][CH2:31][C:28]([NH2:33])([CH2:29][CH2:30]1)[CH2:27][CH2:26]2.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9]2[C:14]([C:15]([NH2:17])=[O:16])=[CH:13][N:12]=[C:11]([NH:33][C:28]34[CH2:31][CH2:32][C:25]([O:24][CH3:23])([CH2:26][CH2:27]3)[CH2:30][CH2:29]4)[N:10]=2)[CH2:3]1

Participants

Conditions

Temperature: 130 °C

Procedure

To a solution of 4-((1R,3S)-3-hydroxycyclohexylamino)-2-(methylsulfonyl)pyrimidine-5-carboxamide (1.2 g, 3.8 mmol; synthesis described herein) and 4-methoxybicyclo[2.2.2]octan-1-amine hydrochloride (600 mg, 3.1 mmol) in NMP (12 mL) was added DIEA (1.03 g, 8 mmol). The resulting mixture was stirred at 130° C. under microwave irradiation for 3 h. The resulting mixture was purified by reverse phase column chromatography to give the desired product (230 mg, 0.6 mmol, 15.5% yield). 1H-NMR (400 MHz, CDCl3) δ ppm 8.70 (brs, 1H), 8.08 (s, 1H), 5.40 (brs, 2H), 5.01 (br. s, 1H), 3.99-3.96 (m, 1H), 3.75-3.70 (m, 1H), 3.19 (s, 3H), 2.37-2.34 (m, 1H), 2.15-2.11 (m, 6H), 1.99-1.97 (m, 2H), 1.90-1.86 (m, 1H), 1.80-1.76 (m, 6H), 1.38-1.22 (m, 4H). MS (ESI) m/z=390.2[M+1]+.

Workup

customsynthesis
customThe resulting mixture was purified by reverse phase column chromatography

Sources & evidence

ORD record: ord-f60a9fc4bb9c4cf5a7afe3b1ed80f665
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139534B2

Reaction notes

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