Formic Acid → 2-Amino-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylic acid

HRID 573603Notes

Reaction equation

HRID 573603 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[C:17]([C:18]([O:20]CC)=[O:19])=[C:16]([CH3:23])[N:15]=[C:14]3[S:24][C:25]([NH:35]C(OC(C)(C)C)=O)=[C:26]([C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=4)[C:13]=23)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+].C(O)=O>CS(C)=O.O>[NH2:35][C:25]1[S:24][C:14]2=[N:15][C:16]([CH3:23])=[C:17]([C:18]([OH:20])=[O:19])[C:12]([NH:11][S:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)(=[O:9])=[O:10])=[C:13]2[C:26]=1[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 14798Sodium HydroxideHCID 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-carboxylate

Product 1

HCID 683238882-Amino-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylic acidYield 81.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 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 (Description 83) (600 mg, 0.949 mmol) and aqueous NaOH (2M) (2.373 mL, 4.75 mmol) in DMSO (10 mL) was heated at 150° C. for 40 min. After cooling to RT, the mixture was diluted with water (20 mL) and acidified with formic acid to pH 6. The mixture was then extracted with ethyl acetate (30 mL×5) and the combined organics concentrated. The residue was passed through a phase separator (C18 cartridge) eluting with water (20 mL×3) and MeOH (20 mL×5) and the combined methanolic fractions concentrated and dried, to give the title compound (388 mg). LCMS (A) m/z: 504 [M+1]+, Rt 1.17 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. extractionThe mixture was then extracted with ethyl acetate (30 mL×5)
  3. washeluting with water (20 mL×3) and MeOH (20 mL×5)
  4. concentrationthe combined methanolic fractions concentrated
  5. customdried

Sources & evidence

ORD record
ord-15d22a9e204946d890286a4015ba16a3
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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