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

HRID 573647Notes

Reaction equation

HRID 573647 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:28]4[CH:29]=[N:30][NH:31][CH:32]=4)=[C:26]([CH3:27])[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:28]4[CH:32]=[N:31][NH:30][CH:29]=4)=[C:26]([CH3:27])[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 68324136Ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-3,6-dimethyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate

Product 1

HCID 683240323-chloro-N-[3,6-dimethyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamideYield 9.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-3,6-dimethyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate (Description 64) (150 mg, 0.306 mmol) in DMSO (5 mL) and aqueous NaOH (2M) (0.611 mL, 3.06 mmol) was heated at 150° C. for ca. 1.5 h. After cooling to RT, the mixture was diluted with water (20 mL), acidified with formic acid (ca. pH 4-5) and extracted with 10% MeOH in DCM (30 mL×5). The combined organics were dried and concentrated. The residue was passed through a C18 solid phase extractor cartridge, eluting with water (30 mL×4) and then with MeOH (30 mL×4) and the combined organics concentrated. The residue was taken-up in diphenyl ether (2 mL, 12.57 mmol) and DMSO (0.5 mL) and the mixture was 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 and then with 0-20% MeOH in DCM and then further purified by MDAP (acidic conditions), to give the title compound (12 mg). LCMS (A) m/z: 419 [M+1]+, Rt 1.04 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. extractionextracted with 10% MeOH in DCM (30 mL×5)
  3. customThe combined organics were dried
  4. concentrationconcentrated
  5. washeluting with water (30 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. customwith 0-20% MeOH in DCM and then further purified by MDAP (acidic conditions)

Sources & evidence

ORD record
ord-3079055eca6f48678e488cb314942f2a
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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