Formic Acid → HCID 68324027, compound

HRID 573574Notes

Reaction equation

HRID 573574 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[N:12][C:13]([CH3:33])=[C:14](C(OCC)=O)[C:15]=3[NH:17][S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)(=[O:20])=[O:19])[S:10][CH:9]=2)[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>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[N:12][C:13]([CH3:33])=[CH:14][C:15]=3[NH:17][S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)(=[O:19])=[O:20])[S:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 284Formic AcidHCID 7583Diphenyl EtherHCID 14798Sodium HydroxideHCID 68323886HCID 68323886, compound

Product 1

HCID 68324027HCID 68324027, compoundYield 67.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of ethyl 3-(3-bromophenyl)-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridine-5-carboxylate (Description 52) (1.4 g, 2.474 mmol) in DMSO (25 mL) and aqueous NaOH (5M) (1.979 mL, 9.90 mmol) was heated at 150° C. for ca. 1 h. After cooling to RT, the mixture was diluted with water (20 mL) and acidified to ca. pH 4 with formic acid. The mixture was then extracted with ethyl acetate (30 mL×3) and the combined organics dried and concentrated. Water (30 mL) was added to the residue and a yellow precipitate crashed-out which was filtered and rinsed with water (15 mL×3). The yellow solid was dried and subsequently taken-up in diphenyl ether (15.74 mL, 99 mmol) and heated at 200° C. for ca. 1.5 h and then allowed to stand at RT overnight. The mixture was purified by chromatography on silica, eluting with a gradient of 0-100% ethyl acetate in cyclohexane followed by 10% MeOH in DCM, to give the title compound (820 mg). LCMS (A) m/z: 494/496 [M+1]+, Rt 1.31 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. extractionThe mixture was then extracted with ethyl acetate (30 mL×3)
  3. customthe combined organics dried
  4. concentrationconcentrated
  5. additionWater (30 mL) was added to the residue
  6. filtrationwas filtered
  7. washrinsed with water (15 mL×3)
  8. temperatureheated at 200° C. for ca. 1.5 h
  9. customThe mixture was purified by chromatography on silica
  10. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-c0f599f6f6804fa4bd0d44cce2743921
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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