Potassium Carbonate → 4-(4-(Cyclopentylamino)-5-(4-hydroxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-3-methoxy-N-methylbenzamide

HRID 1487582노트

반응식

HRID 1487582 반응식
Cl[C:2]1[N:3]=[C:4]([NH:26][CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:5]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:6]=2[N:7]=1.[NH2:32][C:33]1[CH:42]=[CH:41][C:36]([C:37]([NH:39][CH3:40])=[O:38])=[CH:35][C:34]=1[O:43][CH3:44].C(=O)([O-])[O-].[K+].[K+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1.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]>[CH:27]1([NH:26][C:4]2[C:5]3[C:10]([C:11]4[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=4)=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:6]=3[N:7]=[C:2]([NH:32][C:33]3[CH:42]=[CH:41][C:36]([C:37]([NH:39][CH3:40])=[O:38])=[CH:35][C:34]=3[O:43][CH3:44])[N:3]=2)[CH2:31][CH2:30][CH2:29][CH2:28]1

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 204444344-Amino-3-methoxy-N-methylbenzamideHCID 867264174-(2-chloro-4-(cyclopentylamino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenol

생성물 1

HCID 867264184-(4-(Cyclopentylamino)-5-(4-hydroxyphenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-3-methoxy-N-methylbenzamide수율 29.2%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

반응 조건

온도
130 °C

실험 절차

A mixture of 4-(2-chloro-4-(cyclopentylamino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenol (1 equiv), 4-amino-3-methoxy-N-methylbenzamide (1 equiv), potassium carbonate (2.5 equiv), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.2 equiv), and tris(dibenzylideneacetone)-dipalladium (0.2 equiv) in 1,4-dioxane (0.13 M) was purged with nitrogen and sealed. The reaction mixture was heated to 130° C. for 1.5 h. The reaction was filtered and solvents were removed under reduced pressure. The reaction mixture was loaded directly onto a silica gel column and purified using 15-100% ethyl acetate in hexane, followed by 100% ethyl acetate. Fractions containing desired product were combined and volatile organic solvents were removed under reduced pressure to give the title compound (29.2% yield) as a brown oil. MS (ESI) m/z 603.5 [M+1]+.

후처리

  1. customwas purged with nitrogen
  2. customsealed
  3. filtrationThe reaction was filtered
  4. customsolvents were removed under reduced pressure
  5. custompurified
  6. additionFractions containing desired product
  7. customvolatile organic solvents were removed under reduced pressure

출처 및 근거

ORD 기록
ord-9cc6617c397f417b8c4525a9168623c8
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09428509B2

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