Hydrochloric Acid → HCID 86703750, compound

HRID 1849863Notes

Reaction equation

Cl[C:2]1[C:3]([O:12][CH2:13][CH:14]2[CH:19]([CH3:20])[CH2:18][CH2:17][CH2:16][CH:15]2[CH3:21])=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.N12[CH2:44][CH2:43][CH2:42]N=C1CCCCC2.[CH:45]1([S:48]([NH2:51])(=[O:50])=[O:49])[CH2:47][CH2:46]1.Cl>O1CCCC1>[CH:43]1([C:2]2[C:3]([O:12][CH2:13][CH:14]3[CH:19]([CH3:20])[CH2:18][CH2:17][CH2:16][CH:15]3[CH3:21])=[CH:4][C:5]([F:11])=[C:6]([CH:10]=2)[C:7]([NH:51][S:48]([CH:45]2[CH2:47][CH2:46]2)(=[O:50])=[O:49])=[O:9])[CH2:44][CH2:42]1

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of 5-chloro-4-((2,6-dimethylcyclohexyl)methoxy)-2-fluorobenzoic acid (0.07 g, 0.22 mmol) in tetrahydrofuran (2 mL) under an atmosphere of nitrogen was added carbonyldiimidazole (0.053 g, 0.33 mmol). The reaction mixture was stirred at 70° C. for 1 hour. The mixture was cooled to room temperature and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.07 mL, 0.45 mmol) was added followed by cyclopropanesulfonamide (0.045 mg, 0.374 mmol). Stirring continued at room temperature for 18 hours. 5% aqueous hydrochloric acid solution (0.15 mL) was added and the mixture was concentrated and directly purified by column chromatography (0 to 30% ethyl acetate in hexanes) to afford the title compound (0.026 g, 28%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ 12.09-11.90 (m, 1H), 7.71 (d, J=7.07 Hz, 1H), 7.35 (d, J=12.32 Hz, 1H), 4.12-4.06 (m, 2H), 3.11-2.96 (m, 1H), 1.98-0.80 (m, 19H); MS (ES−) m/z 416.2, 418.2 (M−1).

Workup

temperatureThe mixture was cooled to room temperature
stirringStirring
waitcontinued at room temperature for 18 hours
concentrationthe mixture was concentrated
customdirectly purified by column chromatography (0 to 30% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-cb4c64618ac1434e817cec73b21bfa8a
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952169B2

Reaction notes

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