Cesium carbonate → 2-((2-Chloro-5-(difluoromethoxy)-3-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 1430951노트

반응식

HRID 1430951 반응식
Cl[C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:20][CH2:19]2)CC2C=CC(OC)=CC=2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1.[Cl:26][C:27]1[C:33]([N:34]2[CH2:37][CH:36]([N:38]3[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]3)[CH2:35]2)=[CH:32][C:31]([O:45][CH:46]([F:48])[F:47])=[CH:30][C:28]=1[NH2:29].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[Cl:26][C:27]1[C:33]([N:34]2[CH2:35][CH:36]([N:38]3[CH2:39][CH2:40][N:41]([CH3:44])[CH2:42][CH2:43]3)[CH2:37]2)=[CH:32][C:31]([O:45][CH:46]([F:48])[F:47])=[CH:30][C:28]=1[NH:29][C:2]1[N:7]=[C:6]([NH:8][CH:18]2[CH2:19][CH2:20]2)[C:5]2=[N:21][CH:22]=[C:23]([C:24]#[N:25])[N:4]2[N:3]=1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867084772-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile2회HCID 867086602-Chloro-5-(difluoromethoxy)-3-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)aniline

생성물 1

HCID 867086592-((2-Chloro-5-(difluoromethoxy)-3-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile수율 75.9%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 312751,4-Dioxane용매

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온도
105 °C

실험 절차

2-Chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 9) (120 mg, 0.338 mmol), 2-chloro-5-(difluoromethoxy)-3-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)aniline (129 mg, 0.372 mmol), palladium(ii) acetate (22.78 mg, 0.101 mmol), XANTPHOS (19.57 mg, 0.034 mmol), DPPF (18.75 mg, 0.034 mmol) and CESIUM CARBONATE (220 mg, 0.676 mmol) were suspended in Dioxane (3382 μl) at rt. The reaction vessel was evacuated and purged with N2 (4 times) and then heated to 105° C. for 4 h. After cooling to room temperature, the reaction mixture was diluted with EtOAc, filtered through celite and concentrated. Column chromatography (40 g SiO2, 0 to 10% CH3OH—CH2Cl2 gradient elution) afforded the expected product (139.8 mg).

후처리

  1. customThe reaction vessel was evacuated
  2. custompurged with N2 (4 times)
  3. temperatureAfter cooling to room temperature
  4. additionthe reaction mixture was diluted with EtOAc
  5. filtrationfiltered through celite and
  6. concentrationconcentrated
  7. washColumn chromatography (40 g SiO2, 0 to 10% CH3OH—CH2Cl2 gradient elution)

출처 및 근거

ORD 기록
ord-b70fd97e7d0b47689f6db7649a4349d2
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940736B2

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