Isobutylene oxide → 2-[3-(4-Chlorophenyl)ureido]-6-(2-hydroxy-2-methylpropyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide

HRID 1483222Notes

Reaction equation

FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:30])[NH:17][C:18]2[S:26][C:21]3[CH2:22][NH:23][CH2:24][CH2:25][C:20]=3[C:19]=2[C:27]([NH2:29])=[O:28])=[CH:11][CH:10]=1.[CH3:31][C:32]1([CH3:35])[CH2:34][O:33]1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:30])[NH:17][C:18]2[S:26][C:21]3[CH2:22][N:23]([CH2:31][C:32]([OH:33])([CH3:35])[CH3:34])[CH2:24][CH2:25][C:20]=3[C:19]=2[C:27]([NH2:29])=[O:28])=[CH:13][CH:14]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of compound A4 (200 mg, 0.430 mmol), 2,2-dimethyloxirane (155 mg, 2.15 mmol), and diisopropylethylamine (167 mg, 1.29 mmol) in anhydrous N,N-dimethylformamide (1.5 mL) was stirred at room temperature for 2 h and heated to 50° C. in a sealed tube for another 21 h. After this time, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel eluting with 2% to 6% methanol/methylene chloride to afford compound U1 as a yellow solid (36 mg, 20%): 1H NMR (300 MHz, DMSO-d6) δ 10.97 (s, 1H), 10.19 (s, 1H), 7.70-6.70 (m, 6H), 4.19 (s, 1H), 3.62 (s, 2H), 2.78 (bs, 4H), 2.38 (s, 2H), 1.12 (s, 6H). MS (M+H) 423.

Workup

temperatureAfter this time, the reaction mixture was cooled to room temperature
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by flash column chromatography on silica gel eluting with 2% to 6% methanol/methylene chloride

Sources & evidence

ORD record: ord-626d397c025447a196d19e6f673391ed
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09416141B2

Reaction notes

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