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

HRID 573680노트

반응식

HRID 573680 반응식
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.CC1(C)C(C)(C)OB([C:43]2[CH:44]=[C:45]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)[CH:46]=[N:47][CH:48]=2)O1.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:43]4[CH:48]=[N:47][CH:46]=[C:45]([N:49]5[CH2:50][CH2:51][O:52][CH2:53][CH2:54]5)[CH:44]=4)[C:10]=23)(=[O:13])=[O:14])[CH:20]=[CH:19][CH:18]=1

참가 물질

9

반응물 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 584122914-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)morpholineHCID 683240291,1-Dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate

생성물 1

HCID 683239063-Chloro-N-[6-methyl-3-[5-(4-morpholinyl)-3-pyridinyl]-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamide수율 67%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
120 °C

실험 절차

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) (100 mg, 0.171 mmol), 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]morpholine (Description 81) (214 mg, 0.737 mmol), potassium carbonate (71.0 mg, 0.514 mmol), tetrakis(triphenylphosphine)palladium(0) (19.79 mg, 0.017 mmol) and bis(triphenylphosphine)palladium(II) chloride (12.02 mg, 0.017 mmol) were weighed into a microwave vial. 1,4-Dioxane (2 mL), DMF (1 mL) and water (0.5 mL) were added and the mixture heated in a microwave at 120° C. for 15 min. At this point, both mixtures were combined and concentrated. The residue was passed through an SCX cartridge, eluting with MeOH (75 mL) and then with 2M NH3 in MeOH (150 mL). The basic methanolic solution was concentrated and purified by normal phase chromatography, eluting with 0-10% MeOH in DCM, to give the title compound (65 mg). LCMS (A) m/z: 567 [M+1]+, Rt 0.72 min (acidic).

후처리

  1. concentrationconcentrated
  2. washeluting with MeOH (75 mL)
  3. concentrationThe basic methanolic solution was concentrated
  4. custompurified by normal phase chromatography
  5. washeluting with 0-10% MeOH in DCM

출처 및 근거

ORD 기록
ord-9088820950144f0faafcc6ae0dc87e5c
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029545B2

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