2,3,4,5-Tetrahydrobenzo[f][1,4]thiazepine → 4-(4,6-Dimethylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine

HRID 540277Notes

Reaction equation

Cl[C:2]1[CH:11]=[C:10]([CH2:12]C(O)=O)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:16])[CH:8]=2)[N:3]=1.[S:17]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[CH2:21][NH:20][CH2:19][CH2:18]1>C(O)CCC.ClCCl>[CH3:12][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:16])[CH:8]=2)[N:3]=[C:2]([N:20]2[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[S:17][CH2:18][CH2:19]2)[CH:11]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A solution of (2-chloro-6-methylquinolin-4-yl)acetic acid (118 mg, 0.5 mmol) and 2,3,4,5-tetrahydro-1,4-benzothiazepine (247 mg, 1.5 mmol) in n-butanol (0.2 mL) was heated with stirring in a sealed 0.5 mL of microwave process vial for 2 hours at 160° C. After being cooled to room temperature, the reaction mixture was diluted with dichloromethane (50 mL), washed with a saturated aqueous solution of sodium carbonate (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluting with 20-30% ethyl acetate in petroleum ether) to afford 100 mg of the desired product (yield was 62%). MS (ESI+) [(M+H)+] 321.

Workup

temperatureAfter being cooled to room temperature
washwashed with a saturated aqueous solution of sodium carbonate (50 mL) and brine (50 mL)
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel (eluting with 20-30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-85587981e3f84897a13338617f0f3969
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871756B2

Reaction notes

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