Triethylamine → methyl 4-(1,1-dioxidotetrahydro-2H-1,2-thiazin-2-yl)-1H-benzimidazole-6-carboxylate

HRID 852621Notes

Reaction equation

Cl[CH2:2][CH2:3][CH2:4][CH2:5][S:6]([NH:9][C:10]1[C:18]2[N:17]=[CH:16][NH:15][C:14]=2[CH:13]=[C:12]([C:19]([O:21][CH3:22])=[O:20])[CH:11]=1)(=[O:8])=[O:7].CCN(CC)CC>CCO>[O:7]=[S:6]1(=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2][N:9]1[C:10]1[C:18]2[N:17]=[CH:16][NH:15][C:14]=2[CH:13]=[C:12]([C:19]([O:21][CH3:22])=[O:20])[CH:11]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of methyl 4-{[(4-chlorobutyl)sulfonyl]amino}-1H-benzimidazole-6-carboxylate (D252) (1 g, 3.23 mmol, 1 equiv) in EtOH (50 ml) was added NEt3 (2 ml, excess) and the resulting solution was stirred at 70° C. for 2 days. then cooled to room temperature and concentrated in vacuo. The residue was dissolved in AcOEt and the organic phase was washed with a 5% aqueous citric acid solution. The aqueous phase was saturated with NaCl and extracted twice with AcOEt. The combined organic phases were dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (CH2Cl2/MeOH: 96/4 to 90/10) gave methyl 4-(1,1-dioxidotetrahydro-2H-1,2-thiazin-2-yl)-1H-benzimidazole-6-carboxylate (D253) (250 mg, 25%) as a pale yellow solid. [M+H]+=310.3, RT=2.11 min.

Workup

temperaturethen cooled to room temperature
concentrationconcentrated in vacuo
dissolutionThe residue was dissolved in AcOEt
washthe organic phase was washed with a 5% aqueous citric acid solution
extractionextracted twice with AcOEt
dry with materialThe combined organic phases were dried over MgSO4
concentrationconcentrated in vacuo
customPurification of the residue by flash chromatography on silica gel (CH2Cl2/MeOH: 96/4 to 90/10)

Sources & evidence

ORD record: ord-18b70689c5024718b1a9b841eacf5174
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07253198B2

Reaction notes

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