3-(5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazol-1-yl)-N,N-dimethylpropan-1-amine → N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246702

반응식

HRID 246702 반응식
[F:1][CH:2]([F:32])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH2:14][CH2:15][N:16]([CH3:18])[CH3:17])[N:8]=[C:7]2[Sn](CCCC)(CCCC)CCCC.Br[C:34]1[N:39]=[C:38]2[C:40]([C:62]([NH:64][C:65]([CH3:76])([CH3:75])[CH2:66][O:67][Si:68]([C:71]([CH3:74])([CH3:73])[CH3:72])([CH3:70])[CH3:69])=[O:63])=[CH:41][N:42]([C:43]([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:37]2=[N:36][CH:35]=1>CN(C=O)C.[Cu]I.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>[Si:68]([O:67][CH2:66][C:65]([NH:64][C:62]([C:40]1[C:38]2=[N:39][C:34]([C:7]3[C:6]4[C:10](=[CH:11][CH:12]=[C:4]([O:3][CH:2]([F:1])[F:32])[CH:5]=4)[N:9]([CH2:13][CH2:14][CH2:15][N:16]([CH3:17])[CH3:18])[N:8]=3)=[CH:35][N:36]=[C:37]2[N:42]([C:43]([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[C:50]2[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:41]=1)=[O:63])([CH3:75])[CH3:76])([C:71]([CH3:72])([CH3:73])[CH3:74])([CH3:70])[CH3:69]

참가 물질

6

반응물 2

HCID 712800443-(5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazol-1-yl)-N,N-dimethylpropan-1-amineHCID 866780042-bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

생성물 1

HCID 71280050N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide수율 46.6%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

To a solution of 3-(5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazol-1-yl)-N,N-dimethylpropan-1-amine (120 mg, 0.22 mmol) and 2-bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (200 mg, 0.26 mmol) in DMF (10 mL) were added CuI (30 mg, 0.16 mmol) and Pd(PPh3)4 (47 mg, 0.041 mmol), Then the reaction mixture was degassed by bubbling nitrogen for 3 minutes and refilled with nitrogen. The mixture was heated to 80° C. for 5 hours under nitrogen. After cooling to room temperature, water (50 mL) was added and product extracted with EtOAc (3×40 mL), the combined organic layers were dried over Na2SO4, filtered and concentrated to give N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (88 mg, crude) as a yellow oil. LCMS: (M+H)+=858.

후처리

  1. customthe reaction mixture was degassed
  2. customby bubbling nitrogen for 3 minutes
  3. additionrefilled with nitrogen
  4. temperatureAfter cooling to room temperature
  5. additionwater (50 mL) was added
  6. extractionproduct extracted with EtOAc (3×40 mL)
  7. dry with materialthe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-167c63012f184e998dea6447886e2db6
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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