Sodium hydride → HCID 71523440, compound

HRID 1473815Notes

Reaction equation

[F:1][C:2]([F:17])([F:16])[CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([C@H:10]2[CH2:12][C@H:11]2[CH2:13][CH2:14][OH:15])[CH2:6][CH2:5]1.[H-].[Na+].F[C:21]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=1>CN(C=O)C>[CH3:30][S:27]([C:24]1[CH:25]=[CH:26][C:21]([O:15][CH2:14][CH2:13][C@@H:11]2[CH2:12][C@@H:10]2[CH:7]2[CH2:8][CH2:9][N:4]([CH2:3][C:2]([F:1])([F:16])[F:17])[CH2:5][CH2:6]2)=[CH:22][CH:23]=1)(=[O:29])=[O:28]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 2-((1S,2R)-2-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]cyclopropyl)ethanol (30 mg, 0.119 mmol) in DMF (1 mL) was added NaH (60%, 7.2 mg, 0.179 mmol) at RT. The mixture was stirred for 15 min. 1-fluoro-4-(methylsulfonyl)benzene (20.8 mg, 0.119 mmol) was added to the reaction mixture. It was heated at 50° C. for 3 hours. The reaction was quenched with water, extracted with EtOAc. The organic layer was dried by sodium sulfate and concentrated. The residue was purified by Mass directed RPHPLC. The product fraction was basified with 1 M sodium bicarbonate aq. solution, extracted with EtOAc. Solvent was removed under vacuum to yield the Example 4. LCMS calc: 405.47; obs: 406.04 (M+1); Human GPR119 EC50: 175.6 nM. 1H NMR (CDCl3, 500 MHz) 7.90 (d, 2H), 7.02 (d, 2H), 4.15 (m, 2H), 3.05 (s, 3H), 2.97 (m, 4), 2.34 (m, 2H), 2.18 (m, 1H), 1.78 (m, 2H), 1.45-1.58 (m, 3H), 0.96 (m, 1H), 0.82 (m, 1H), 0.65 (m, 2H), −0.88 (m, 1H)

Workup

customThe reaction was quenched with water
extractionextracted with EtOAc
dry with materialThe organic layer was dried by sodium sulfate
concentrationconcentrated
customThe residue was purified by Mass
extractionextracted with EtOAc
customSolvent was removed under vacuum
customto yield the Example 4

Sources & evidence

ORD record: ord-70964d569f954d44b6dc334d28f0417f
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018200B2

Reaction notes

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