Sulfuryl chloride → 5-Chloro-3-(2,5-dichloro-pyrimidin-4-ylamino)-4-methyl-thiophene-2-carboxylic acid methylamide
Reaction equation
[CH3:1][NH:2][C:3]([C:5]1[S:6][CH:7]=[C:8]([CH3:19])[C:9]=1[NH:10][C:11]1[C:16]([Cl:17])=[CH:15][N:14]=[C:13]([Cl:18])[N:12]=1)=[O:4].S(Cl)([Cl:23])(=O)=O>C(Cl)Cl>[CH3:1][NH:2][C:3]([C:5]1[S:6][C:7]([Cl:23])=[C:8]([CH3:19])[C:9]=1[NH:10][C:11]1[C:16]([Cl:17])=[CH:15][N:14]=[C:13]([Cl:18])[N:12]=1)=[O:4]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
An ice-cold solution of 3-(2,5-dichloro-pyrimidin-4-ylamino)-4-methyl-thiophene-2-carboxylic acid methylamide (0.105 g, 0.33 mmol) in methylene chloride (4 mL) was treated with sulfuryl chloride (33 μL). The mixture was stirred for 16 hours and concentrated. Chromatography on preparative TLC plate (hexanes/ethyl acetate/methanol (50:25:1)) gave 5-chloro-3-(2,5-dichloro-pyrimidin-4-ylamino)-4-methyl-thiophene-2-carboxylic acid methylamide (10.4 mg, 9%): 1H NMR (300 MHz, CDCl3) δ 9.9 (s, 1H), 8.33 (s, 1H), 5.82 (br, 1H), 3.05 (d, 3H), 2.22 (s, 3H); MS (m/e): 351.1 (M+1). 1770b) Following a procedure analogous to Example 1741e, 5-chloro-3-(2,5-dichloro-pyrimidin-4-ylamino)-4-methyl-thiophene-2-carboxylic acid methylamide and 2-amino-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one were converted to 5-chloro-3-[5-chloro-2-(5-methyl-6-oxo-5,6,8,9-tetrahydro-7-oxa-5-aza-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-4-methyl-thiophene-2-carboxylic acid methylamide: 1H NMR (300 MHz, CDCl3) δ 8.77 (s, 1H), 8.07 (br, 1H), 7.37 (d, 1H), 7.2 (dd, 1H), 7.15 (br, 1H), 7.0 (d, 1H), 5.85 (q, 1H), 4.43 (t, 2H), 3.33 (s, 3H), 2.92 (d, 3H), 2.85 (t, 2H), 2.0 (s, 3H); MS (m/e): 507.2 (M+1).
Workup
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-1372c0a2b75740ea81fd602359756d9f
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08552186B2
Reaction notes
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