Phenylphosphonic dichloride → 3-Chloro-N-{6-chloro-2-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[C:13]3[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)=[C:20]([CH3:30])[S:19][C:14]=3[NH:15][C:16](=O)[CH:17]=2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.C1(P(Cl)([Cl:39])=O)C=CC=CC=1>>[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[CH:17]=[C:16]([Cl:39])[N:15]=[C:14]3[S:19][C:20]([CH3:30])=[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=4)[C:13]=23)(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=1Participants
Procedure
A solution of 3-chloro-N-{2-methyl-3-[3-(methyloxy)phenyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridin-4-yl}benzenesulfonamide (Example 116) (150 mg, 0.325 mmol) in phenylphosphonic dichloride (1.5 mL, 10.72 mmol) was heated to 200° C. under a nitrogen atmosphere. The reaction mixture was cooled to RT, poured dropwise onto ice and left for ca. 30 min. The aqueous layer was extracted with DCM (ca. 25 mL×2), the combined organics passed through phase separator and the solvent removed in vacuo. The residue was then purified by normal phase chromatography, eluting with a gradient of 0-50% ethyl acetate in cyclohexane and then further purified by MDAP (acidic conditions), to afford the title compound (37 mg). LCMS (A) m/z: 479 [M+1]+, Rt 1.62 min (acidic).
Workup
- additionpoured dropwise onto ice
- extractionThe aqueous layer was extracted with DCM (ca. 25 mL×2)
- customthe solvent removed in vacuo
- customThe residue was then purified by normal phase chromatography
- washeluting with a gradient of 0-50% ethyl acetate in cyclohexane
- customfurther purified by MDAP (acidic conditions)
Sources & evidence
- ORD record
- ord-eb6adadda9f1416e892d63b6de48d85f
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09029545B2
Reaction notes
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