Formic Acid → 3-chloro-N-[6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamide

HRID 573670Notes

Reaction equation

HRID 573670 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[C:17](C(OCC)=O)=[C:16]([CH3:23])[N:15]=[C:14]3[S:24][C:25]([C:27]4[CH:28]=[N:29][NH:30][CH:31]=4)=[CH:26][C:13]=23)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+].C(O)=O.C1(OC2C=CC=CC=2)C=CC=CC=1>CS(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[CH:17]=[C:16]([CH3:23])[N:15]=[C:14]3[S:24][C:25]([C:27]4[CH:28]=[N:29][NH:30][CH:31]=4)=[CH:26][C:13]=23)(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 284Formic AcidHCID 7583Diphenyl EtherHCID 14798Sodium HydroxideHCID 68380155Ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate

Product 1

HCID 683241633-chloro-N-[6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamideYield 23.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate (Description 73) (250 mg, 0.524 mmol) in DMSO (5 mL) and aqueous NaOH (2M) (1.048 mL, 5.24 mmol) was heated at 150° C. for ca. 1 h. After cooling to RT, the mixture was diluted with water (20 mL) and acidified with formic acid (pH ca. 4-5). The mixture was extracted with 10% MeOH in DCM (30 mL×5) and the combined organics dried and concentrated. The residue was passed through a C18 solid phase extractor cartridge, eluting with water (100 mL×4) and then with MeOH (100 mL×4) and the combined organics concentrated. The residue was taken-up in diphenyl ether (2.501 mL, 15.72 mmol) and DMSO (0.5 mL) and the mixture heated at 200° C. for ca. 45 min. After cooling to RT, the mixture was purified by normal phase chromatography, eluting with a gradient of 0-100% ethyl acetate in cyclohexane followed by a gradient of 0-10% MeOH in DCM and then further purified by MDAP (basic conditions), to give the title compound (49 mg). LCMS (A) m/z: 405 [M+1]+, Rt 0.98 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. extractionThe mixture was extracted with 10% MeOH in DCM (30 mL×5)
  3. customthe combined organics dried
  4. concentrationconcentrated
  5. washeluting with water (100 mL×4)
  6. temperatureAfter cooling to RT
  7. customthe mixture was purified by normal phase chromatography
  8. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane
  9. customfurther purified by MDAP (basic conditions)

Sources & evidence

ORD record
ord-8117ef0e1fd843ecbb9456aa20bcdc91
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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