Dimethylformamide → 3-Chloro-N-{6-methyl-2-(1H-pyrazol-4-yl)-3-[3-(1-pyrrolidinyl)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide

HRID 573678노트

반응식

HRID 573678 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[CH2:53][CH2:52][CH2:51][CH2:50]3)[CH:46]=[CH:47][CH:48]=2)O1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>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>[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:47]4[CH:48]=[CH:43][CH:44]=[C:45]([N:49]5[CH2:50][CH2:51][CH2:52][CH2:53]5)[CH:46]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

참가 물질

8

반응물 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 185257431-[3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrrolidineHCID 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 683237583-Chloro-N-{6-methyl-2-(1H-pyrazol-4-yl)-3-[3-(1-pyrrolidinyl)phenyl]thieno[2,3-b]pyridin-4-yl}benzenesulfonamide수율 6.1%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

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) (350 mg, 0.599 mmol), 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrrolidine (327 mg, 1.2 mmol), tetrakis(triphenylphosphine)palladium(0) (34.6 mg, 0.03 mmol), bis(triphenylphosphine)palladium(II) chloride (21.04 mg, 0.030 mmol) and potassium carbonate (249 mg, 1.8 mmol) were charged into a microwave vial. DMF (2.5 mL) and water (1.0 mL) were added and the suspension degassed under nitrogen for ca. 5 min before being subjected to heating in a microwave at 100° C. for 30 min. The reaction mixture was then filtered through celite, rinsed with ethyl acetate (ca. 50 mL) and the solvent removed in vacuo. Purification by chromatography on silica, eluting with a gradient of 0-40% ethyl acetate in DCM followed by 0-20% MeOH in DCM and then further purification by MDAP (acidic conditions) afforded the title compound (20 mg). LCMS (A) m/z: 550 [M+1]+, Rt 1.30 min (basic).

후처리

  1. customthe suspension degassed under nitrogen for ca. 5 min
  2. filtrationThe reaction mixture was then filtered through celite
  3. washrinsed with ethyl acetate (ca. 50 mL)
  4. customthe solvent removed in vacuo
  5. customPurification by chromatography on silica
  6. washeluting with a gradient of 0-40% ethyl acetate in DCM
  7. customfurther purification by MDAP (acidic conditions)

출처 및 근거

ORD 기록
ord-3e2c9455f7804d5f8688fafb65a708c5
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029545B2

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