Ethyl orthoformate → 6-((5-(benzyloxy)-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole

HRID 1848161Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([NH2:28])[C:12]([NH:15][CH2:16][C:17]2[CH:27]=[CH:26][C:20]3[N:21]=[C:22]([S:24][CH3:25])[S:23][C:19]=3[CH:18]=2)=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:29](OC(OCC)OCC)C>C(O)=O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]2[N:15]([CH2:16][C:17]3[CH:27]=[CH:26][C:20]4[N:21]=[C:22]([S:24][CH3:25])[S:23][C:19]=4[CH:18]=3)[CH:29]=[N:28][C:11]=2[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 4-(benzyloxy)-N1-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)benzene-1,2-diamine (2.49 g, 6.1 mmol) from the previous step, triethylorthoformate (60 mL), and formic acid (1.22 g) was stirred at 90° C. for 2 h. The reaction mixture was cooled to rt, and then concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with a gradient of 50% EtOAc in petroleum ether to 100% EtOAc to afford 6-((5-(benzyloxy)-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylthio)benzo[d]thiazole (1.6 g, 62%) as a light yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.93 (s, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.50 (s, 1H), 7.44-7.49 (m, 2H), 7.30-7.40 (m, 4H), 7.26 (m, 1H), 7.13 (d, J=9.0 Hz, 1H), 6.98 (m, 1H), 5.41 (s, 2H), 5.10 (s, 2H), 2.77 (s, 3H); LCMS (ESI) m/z 418 (M+H)+.

Workup

temperatureThe reaction mixture was cooled to rt
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel flash chromatography
washeluting with a gradient of 50% EtOAc in petroleum ether to 100% EtOAc

Sources & evidence

ORD record: ord-fbf80047a9ac4cc7bd283b1cac24faf7
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952058B2

Reaction notes

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