4-Aminobenzonitrile → 4-(5-(3-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

HRID 1042291

반응식

HRID 1042291 반응식
[NH:1]1[C:5]2=[N:6][CH:7]=[N:8][C:9]([C:10]3[C:11]([NH:16][C:17]4[C:18]5[CH:19]=[CH:20][N:21]=[C:22](Cl)[C:23]=5[CH:24]=[CH:25][C:26]=4[CH3:27])=[N:12][CH:13]=[CH:14][CH:15]=3)=[C:4]2[CH:3]=[N:2]1.[NH2:29][C:30]1[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=1.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCN(CC)CC.CC(O)=O.C(Cl)Cl>[NH:1]1[C:5]2=[N:6][CH:7]=[N:8][C:9]([C:10]3[C:11]([NH:16][C:17]4[C:26]([CH3:27])=[CH:25][CH:24]=[C:23]5[C:18]=4[CH:19]=[CH:20][N:21]=[C:22]5[NH:29][C:30]4[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[CH:32][CH:31]=4)=[N:12][CH:13]=[CH:14][CH:15]=3)=[C:4]2[CH:3]=[N:2]1

참가 물질

10

반응물 4

HCID 133964-AminobenzonitrileHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 59627378N-(3-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine

생성물 1

HCID 596273694-(5-(3-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

시약·촉매·용매 5

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 176Acetic Acid용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매

반응 조건

온도
100 °C

실험 절차

A mixture of N-(3-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine (160 mg, 413 mmol), 4-aminobenzonitrile (53.6 mg, 454 μmol), tris(dibenzylideneacetone)dipalladium(0) (18.9 mg, 20.6 μmol) and DavePhos (17.9 mg, 45.4 mmol) in THF (3 ml) was slightly vacuumed to de-gas, and then lithium bis(trimethylsilyl)amide (1.0 M solution in THF) (1857 μl, 1857 μmol) was added and the microwave tube was sealed under N2 gas. The mixture was heated in a microwave reactor at 100° C. for 30 min. The mixture was poured into DCM (10 ml)-AcOH (0.5 ml) and stirred for 10 min, then Et3N (0.5 ml) was added. Solvent was removed under vacuum and the residue was purified by flash chromatography eluting with MeOH/DCM (1-4%) to give 4-(5-(3-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile. MS Found: (ESI pos. ion) m/z 470 (M+H+).

후처리

  1. customto de-gas
  2. customthe microwave tube was sealed under N2 gas
  3. customSolvent was removed under vacuum
  4. customthe residue was purified by flash chromatography
  5. washeluting with MeOH/DCM (1-4%)

출처 및 근거

ORD 기록
ord-611d0bbcb6d248ef86692eecb1bbedda
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08557830B2

연결된 노트

불러오는 중…