Potassium Carbonate → 3-Chloro-N-[3-[5-(dimethylamino)-3-pyridinyl]-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamide

HRID 573682Notes

Reaction equation

HRID 573682 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:22])=[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:23]1[CH:24]=[N:25][N:26](C(OC(C)(C)C)=O)[CH:27]=1.[CH3:35][N:36]([C:38]1[C:39](B(O)O)=[N:40][CH:41]=[CH:42][CH:43]=1)[CH3:37].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>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[C:7]([CH3:22])[N:6]=[C:5]3[S:4][C:3]([C:23]4[CH:27]=[N:26][NH:25][CH:24]=4)=[C:2]([C:42]4[CH:41]=[N:40][CH:39]=[C:38]([N:36]([CH3:37])[CH3:35])[CH:43]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 67236313Dimethylamino pyridine boronic acidHCID 683240291,1-Dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate

Product 1

HCID 683239083-Chloro-N-[3-[5-(dimethylamino)-3-pyridinyl]-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamideYield 46.7%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
110 °C

Procedure

A mixture of 1,1-dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate (Description 75) (150 mg, 0.257 mmol), dimethylamino pyridine boronic acid (85 mg, 0.514 mmol), potassium carbonate (107 mg, 0.771 mmol), tetrakis(triphenylphosphine)palladium(0) (7.42 mg, 6.42 μmol) and bis(triphenylphosphine)palladium(II) chloride (4.51 mg, 6.42 μmol) were weighed into a microwave vial. 1,4-Dioxane (2.0 mL), DMF (1.0 mL) and water (0.5 mL) were added and the mixture heated in a microwave at 110° C. for 30 min. At this point, both reaction mixtures were combined and concentrated. The residue was passed through an SCX cartridge, eluting with MeOH (100 mL) and then with 2M NH3 in MeOH (150 mL). The basic methanolic solution was concentrated and purified by MDAP (acidic conditions) and then further purified by normal phase chromatography, eluting with a gradient of 0-10% MeOH in DCM, to give the title compound (63 mg). LCMS (A) m/z: 523 [M−1]−, Rt 0.78 min (acidic).

Workup

  1. customAt this point, both reaction mixtures
  2. concentrationconcentrated
  3. washeluting with MeOH (100 mL)
  4. concentrationThe basic methanolic solution was concentrated
  5. custompurified by MDAP (acidic conditions)
  6. customfurther purified by normal phase chromatography
  7. washeluting with a gradient of 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-2d36d09c6c2f4f86af0cfca92a165160
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

Loading…