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

HRID 573590Notes

Reaction equation

HRID 573590 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:26])=[C:8](C(OCC)=O)[C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[C:27]1[CH:28]=[N:29][NH:30][CH:31]=1.[OH-].[Na+].C1(OC2C=CC=CC=2)C=CC=CC=1.N1C2C(=CC=CC=2)C=CC=1>CS(C)=O.O.C(O)=O>[Br:1][C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:26])=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[C:27]1[CH:28]=[N:29][NH:30][CH:31]=1

Participants

8

Reactant 4

HCID 7047QuinolineHCID 7583Diphenyl EtherHCID 14798Sodium HydroxideHCID 68324120ethyl 3-bromo-6-methyl-4-[(phenylsulfonyl)amino]-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate

Product 1

HCID 68324061N-[3-bromo-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamideYield 54.8%

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolventHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of ethyl 3-bromo-6-methyl-4-[(phenylsulfonyl)amino]-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate (Description 69) (6.1 g, 11.70 mmol) in DMSO (120 mL) and aqueous NaOH (5M) (9.36 mL, 46.8 mmol) was heated at 150° C. for ca. 2.5 h. After cooling to RT, the mixture was diluted with water (100 mL) and acidified with formic acid. The mixture was extracted with 20% MeOH in DCM (75 mL×5) and the combined organics dried and concentrated. Water (100 mL) was added to the residue and a precipitate crashed-out which was filtered and rinsed with water (50 mL×3). The solid was dried and then taken-up in diphenyl ether (74.4 mL, 468 mmol) and quinoline (13.86 mL, 117 mmol). The resulting mixture was then heated at 200° C. for ca. 5 h. After cooling to RT, the mixture was purified via normal phase chromatography, eluting with 0-100% ethyl acetate in DCM, to give the title compound (2.88 g). LCMS (A) m/z: 449/451 [M+1]+, Rt 1.05 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. extractionThe mixture was extracted with 20% MeOH in DCM (75 mL×5)
  3. customthe combined organics dried
  4. concentrationconcentrated
  5. additionWater (100 mL) was added to the residue
  6. filtrationwas filtered
  7. washrinsed with water (50 mL×3)
  8. customThe solid was dried
  9. temperatureThe resulting mixture was then heated at 200° C. for ca. 5 h
  10. temperatureAfter cooling to RT
  11. customthe mixture was purified via normal phase chromatography
  12. washeluting with 0-100% ethyl acetate in DCM

Sources & evidence

ORD record
ord-d50c31bc65d348179b6e1c03538e0dbe
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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