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 529642노트

반응식

HRID 529642 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

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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 hexanes, 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-a268a17543bd42b0b22dd2b77e14672d
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346812B2

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