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

HRID 573671Notes

Reaction equation

HRID 573671 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:27])=[C:8](C(OCC)=O)[C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[C:28]1[CH:29]=[N:30][NH:31][CH:32]=1.[OH-].[Na+].C(O)=O.C1(OC2C=CC=CC=2)C=CC=CC=1>CS(C)=O.O>[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:27])=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[C:28]1[CH:32]=[N:31][NH:30][CH:29]=1

Participants

7

Reactant 4

HCID 284Formic AcidHCID 7583Diphenyl EtherHCID 14798Sodium HydroxideHCID 68380308ethyl 3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate

Product 1

HCID 68324082N-[3-bromo-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamideYield 53.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of ethyl 3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate (Description 74) (920 mg, 1.65 mmol) in DMSO (15 mL) and aqueous NaOH (5M) (3.31 mL, 16.55 mmol) was heated at 150° C. for ca. 1.5 h. After cooling to RT, the mixture was diluted with water (20 mL) and acidified with formic acid (ca. pH 4-5). The mixture was extracted with 10% MeOH/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 (877 mg) was taken-up in diphenyl ether (5.0 mL, 31.4 mmol) and DMSO (0.5 mL) and the mixture heated at 200° C. for ca. 1 h. After cooling to RT, the mixture was purified by chromatography on silica, eluting with a gradient of 0-100% ethyl acetate in cyclohexane, to give the title compound (430 mg). LCMS (A) m/z: 483/485 [M+1]+, Rt 1.16 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. extractionThe mixture was extracted with 10% MeOH/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 chromatography on silica
  8. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-9c46c317757c43da9d1b2ebabe39facf
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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