Hydrochloric Acid → HCID 71078002, compound

HRID 1774483Notes

Reaction equation

C[O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([S:10][C:11]2[C:19]3[C:14](=[CH:15][C:16]([Cl:20])=[CH:17][CH:18]=3)[NH:13][C:12]=2[CH3:21])[CH:7]=[N:6][CH:5]=1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[H-].[Na+].Cl>CN(C=O)C.C1COCC1>[CH2:23]([N:13]1[C:14]2[C:19](=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)[C:11]([S:10][C:8]2[CH:7]=[N:6][CH:5]=[C:4]([CH:9]=2)[C:3]([OH:2])=[O:22])=[C:12]1[CH3:21])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 0 °C

Procedure

5-(6-Chloro-2-methyl-1H-indol-3-ylsulfanyl)-nicotinic acid methyl ester and benzyl bromide (0.0267 mL, 0.225 mmol) were dissolved in DMF:THF (1:1, 4 mL). The mixture was cooled to 0° C., sodium hydride (60% in mineral oil, 0.015 g, 0.375 mmol) was added, and the ice bath was removed. After warming to room temperature, the reaction was heated to 50° C. for 1 hour. Analytical LCMS indicated complete conversion and, furthermore, complete hydrolysis of the methyl ester. The reaction was neutralized with HCl (aq.), diluted with EtOAc/hexanes and washed with H2O/brine. The organic portion was dried and concentrated and the residue was purified via preparatory HPLC (10-100% ACN in H2O, 20 minute run, r.t.=13.1 minutes) to give the title compound. Mass spectrometric data: [M+H]+=409.

Workup

customthe ice bath was removed
temperatureAfter warming to room temperature
temperaturethe reaction was heated to 50° C. for 1 hour
customfurthermore, complete hydrolysis of the methyl ester
washwashed with H2O/brine
customThe organic portion was dried
concentrationconcentrated
customthe residue was purified via preparatory HPLC (10-100% ACN in H2O, 20 minute run, r.t.=13.1 minutes)

Sources & evidence

ORD record: ord-ca86423b7182499c80de2c7ae469f7df
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260416B2

Reaction notes

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