Cesium carbonate → 3-Chloro-N-[6-methyl-3-[3-(methyloxy)phenyl]-2-(1-pyrrolidinyl)thieno[2,3-b]pyridin-4-yl]-benzenesulfonamide

HRID 573620Notes

Reaction equation

HRID 573620 reaction equation
Br[C:2]1[S:22][C:5]2=[N:6][C:7]([CH3:21])=[CH:8][C:9]([NH:10][S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=3)(=[O:13])=[O:12])=[C:4]2[C:3]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=1.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:20][C:16]1[CH:15]=[C:14]([S:11]([NH:10][C:9]2[CH:8]=[C:7]([CH3:21])[N:6]=[C:5]3[S:22][C:2]([N:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)=[C:3]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=4)[C:4]=23)(=[O:13])=[O:12])[CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 31268PyrrolidineHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 53250396N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamide

Product 1

HCID 683241503-Chloro-N-[6-methyl-3-[3-(methyloxy)phenyl]-2-(1-pyrrolidinyl)thieno[2,3-b]pyridin-4-yl]-benzenesulfonamideYield 8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of N-{2-bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamide (50 mg, 0.095 mmol) (Example 33), pyrrolidine (0.039 mL, 0.477 mmol), Pd2(dba)3 (8.74 mg, 9.54 μmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (8.11 mg, 0.019 mmol) and Cs2CO3 (93 mg, 0.286 mmol) in THF (1 mL) was heated at 70° C. for 19 h. The mixture was then filtered through celite and the filtrate concentrated. Purification by chromatography on silica gel, eluting with a gradient of 20-50% ethyl acetate in DCM was followed by further purification by MDAP (acidic conditions), to give the title compound (3.9 mg). LCMS (A) m/z: 514 [M+1]+, Rt 1.56 min (acidic), Rt 1.09 min (basic).

Workup

  1. filtrationThe mixture was then filtered through celite
  2. concentrationthe filtrate concentrated
  3. customPurification by chromatography on silica gel
  4. washeluting with a gradient of 20-50% ethyl acetate in DCM
  5. customwas followed by further purification by MDAP (acidic conditions)

Sources & evidence

ORD record
ord-35ecc146ecf94fa7a750b6838bb856ab
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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