Cesium carbonate → 5-(1h-Benzoimidazol-2-ylamino)-3-cyclohexylmethoxy-isothiazole-4-carboxylic acid amide monoformate salt

HRID 1178697Notes

Reaction equation

[CH:1]1([CH2:7][O:8][C:9]2[C:13]([C:14]([NH2:16])=[O:15])=[C:12](SC)[S:11][N:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:19]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[N:21]=[C:20]1[NH2:28].[C:29](=O)([O-:31])[O-:30].[Cs+].[Cs+]>CN(C=O)C>[CH:29]([OH:31])=[O:30].[NH:19]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[N:21]=[C:20]1[NH:28][C:12]1[S:11][N:10]=[C:9]([O:8][CH2:7][CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:13]=1[C:14]([NH2:16])=[O:15]

Participants

Conditions

Temperature: 100 °C

Procedure

3-Cyclohexylmethoxy-5-methylsulfanyl-isothiazole-4-carboxylic acid amide (5) (30 mg, 0.094 mmol) is dissolved in DMF (0.3 mL) and the solution is agitated on a shaker plate. 1H-Benzoimidazol-2-ylamine (25 mg, 0.188 mmol) and cesium carbonate (61 mg, 0.188 mmol) are then added and the reaction mixture is heated to 100° C. and agitated for 4 hrs. The resulting solution is then filtered and the mother liquor is purified by preparative HPLC to provide 5-(1H-Benzoimidazol-2-ylamino)-3-cyclohexylmethoxy-isothiazole-4-carboxylic acid amide monoformate salt (1.0 mg). 1H NMR (d6 DMSO): δ 12.09 (1H, s), 11.88 (1H, s), 7.77 (1H, s), 7.45–7.47 (1H, m), 7.36–7.38 (1H, m), 7.05–7.10 (2H, m), 7.01 (1H, s), 4.19 (2H, d, J=6.4 Hz), 1.61–1.83 (6H, m), 1.14–1.31 (3H, m), 0.97–1.11 (2H, m); LRMS (M+): 372.1.

Workup

stirringagitated for 4 hrs
filtrationThe resulting solution is then filtered
customthe mother liquor is purified by preparative HPLC

Sources & evidence

ORD record: ord-7b87edfb758d4a7686de7cd3b6536d6c
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07276602B2

Reaction notes

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