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

HRID 573672Notes

Reaction equation

HRID 573672 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 Hydroxide2×HCID 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 42.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

Alternatively, 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) (8.2 g, 14.75 mmol) in DMSO (150 mL) and aqueous NaOH (5M) (11.80 mL, 59.0 mmol) was heated at 150° C. for ca. 15 min. Extra aqueous NaOH (5M) (11.80 mL, 59.0 mmol) was added and the mixture heated at 150° C. for another 45′ min. After cooling to RT, the mixture was diluted with water (200 mL) and acidified with formic acid (ca. pH 4-5). The mixture was then extracted with 20% MeOH/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 collected by filtration and rinsed with water (50 mL×3). The solid was dried and subsequently taken-up in diphenyl ether (100 mL, 629 mmol) and DMSO (20 mL) and the mixture heated at 200° C. for ca. 35 min. After cooling to RT, the mixture was purified on silica, eluting with a gradient of 0-100% ethyl acetate in cyclohexane followed by 10% MeOH in DCM, to give the title compound (3.03 g).

Workup

  1. temperaturethe mixture heated at 150° C. for another 45′ min
  2. temperatureAfter cooling to RT
  3. extractionThe mixture was then extracted with 20% MeOH/DCM (75 mL×5)
  4. customthe combined organics dried
  5. concentrationconcentrated
  6. additionWater (100 mL) was added to the residue
  7. filtrationwas collected by filtration
  8. washrinsed with water (50 mL×3)
  9. temperaturethe mixture heated at 200° C. for ca. 35 min
  10. temperatureAfter cooling to RT
  11. customthe mixture was purified on silica
  12. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-98c48ef9be99412bbdd0c92c0cc44d80
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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