3-Chlorobenzenesulphonyl chloride → Ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylate

HRID 573602Notes

Reaction equation

HRID 573602 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH3:13])[N:5]=[C:4]2[S:14][C:15]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=3)[C:3]=12.CC(C)([O-])C.[Na+].[Cl:39][C:40]1[CH:41]=[C:42]([S:46](Cl)(=[O:48])=[O:47])[CH:43]=[CH:44][CH:45]=1.[NH4+].[Cl-]>C1COCC1>[Cl:39][C:40]1[CH:41]=[C:42]([S:46]([NH:1][C:2]2[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH3:13])[N:5]=[C:4]3[S:14][C:15]([NH:25][C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])=[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=4)[C:3]=23)(=[O:48])=[O:47])[CH:43]=[CH:44][CH:45]=1

Participants

6

Reactant 4

HCID 179093-Chlorobenzenesulphonyl chlorideHCID 25517Ammonium ChlorideHCID 23676156Sodium t-butoxideHCID 68380693Ethyl 4-amino-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylate

Product 1

HCID 68380565Ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylateYield 28.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 4-amino-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylate (Description 82) (1.54 g, 3.37 mmol) in THF (30 mL) was added sodium tert-butoxide (1.294 g, 13.46 mmol) at RT and the mixture stirred for 15 min before 3-chlorobenzenesulfonyl chloride (0.948 mL, 6.73 mmol) was added. The resulting mixture was then stirred for ca. 3.5 h. Saturated NH4Cl solution (50 mL) was then added to the mixture which was extracted with ethyl acetate (30 mL×3). The combined organics were washed with brine (30 mL), dried and concentrated. The residue was purified by normal phase chromatography, eluting with a gradient of 0-30% ethyl acetate in cyclohexane, to give the title compound (600 mg). LCMS (A) m/z: 632 [M+1]+, Rt 1.74 min (acidic).

Workup

  1. additionwas added
  2. extractionwas extracted with ethyl acetate (30 mL×3)
  3. washThe combined organics were washed with brine (30 mL)
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by normal phase chromatography
  7. washeluting with a gradient of 0-30% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-df625a922e524941918ca7fe7b757cac
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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