Potassium Carbonate → N-{6-Methyl-2-(1H-pyrazol-4-yl)-3-[5-(1-pyrrolidinyl)-3-pyridinyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide

HRID 573686Notes

Reaction equation

HRID 573686 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:21])=[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:22]1[CH:23]=[N:24][N:25](C(OC(C)(C)C)=O)[CH:26]=1.[N:34]1([C:39]2[CH:40]=[N:41][CH:42]=[C:43](B3OC(C)(C)C(C)(C)O3)[CH:44]=2)[CH2:38][CH2:37][CH2:36][CH2:35]1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CN(C=O)C>[CH3:21][C:7]1[N:6]=[C:5]2[S:4][C:3]([C:22]3[CH:23]=[N:24][NH:25][CH:26]=3)=[C:2]([C:43]3[CH:42]=[N:41][CH:40]=[C:39]([N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)[CH:44]=3)[C:10]2=[C:9]([NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])[CH:8]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 584122943-(Pyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 683241281,1-Dimethylethyl 4-{3-bromo-6-methyl-4-[(phenylsulfonyl)amino]thieno[2,3-b]pyridin-2-yl}-1H-pyrazole-1-carboxylate

Product 1

HCID 68324055N-{6-Methyl-2-(1H-pyrazol-4-yl)-3-[5-(1-pyrrolidinyl)-3-pyridinyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamideYield 98.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1,1-dimethylethyl 4-{3-bromo-6-methyl-4-[(phenylsulfonyl)amino]thieno[2,3-b]pyridin-2-yl}-1H-pyrazole-1-carboxylate (Description 71) (200 mg, 0.364 mmol), 3-(1-pyrrolidinyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Description 79) (399 mg, 0.73 mmol), potassium carbonate (151 mg, 1.09 mmol), tetrakis(triphenylphosphine)palladium(0) (42.1 mg, 0.036 mmol) and bis(triphenylphosphine)palladium(II) chloride (25.5 mg, 0.036 mmol) were weighed into a microwave vial. 1,4-Dioxane (3 mL), DMF (1.5 mL) and water (0.75 mL) were added and the mixture heated in a microwave at 120° C. for 30 min. At this point, all three reaction mixtures were combined and concentrated. The residue was passed through an SCX cartridge, eluting with MeOH (150 mL) and then with 2M NH3 in MeOH (200 mL). The basic methanolic solution was concentrated and purified by normal phase chromatography, eluting with 0-100% ethyl acetate in DCM, followed by trituration with DCM (10 mL×3), to give the title compound (185 mg). LCMS (A) m/z: 517 [M+1]+, Rt 0.76 min (acidic).

Workup

  1. customAt this point, all three reaction mixtures
  2. concentrationconcentrated
  3. washeluting with MeOH (150 mL)
  4. concentrationThe basic methanolic solution was concentrated
  5. custompurified by normal phase chromatography
  6. washeluting with 0-100% ethyl acetate in DCM

Sources & evidence

ORD record
ord-8da8140213664e8c8c376a3db0d61823
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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