2-Methyltetrahydrofuran → (R)-methyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate

HRID 1055038노트

반응식

HRID 1055038 반응식
CC1OCCC1.[F:7][C:8]1[CH:9]=[C:10]2[C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][N:14]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:11]2=[N:12][CH:13]=1.Cl[C:37]1[N:42]=[C:41]([NH:43][C@@H:44]([C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:45][C:46]([O:48][CH3:49])=[O:47])[C:40]([F:54])=[CH:39][N:38]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].O>[F:54][C:40]1[C:41]([NH:43][C@@H:44]([C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:45][C:46]([O:48][CH3:49])=[O:47])=[N:42][C:37]([C:16]2[C:10]3[C:11](=[N:12][CH:13]=[C:8]([F:7])[CH:9]=3)[N:14]([S:26]([C:29]3[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=3)(=[O:28])=[O:27])[CH:15]=2)=[N:38][CH:39]=1

참가 물질

8

반응물 5

HCID 73012-MethyltetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672856905-fluoro-1-((4-methylphenyl)sulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 86714731methyl (3R)-3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-4,4-dimethylpentanoate

생성물 1

HCID 71247937(R)-methyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매

반응 조건

온도
115 °C

실험 절차

A 2-MeTHF (253 mL)/water (56 mL) solution of 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 7a, (24.3 g, 58.3 mmol), methyl (R)-methyl 3-((2-chloro-5-fluoropyrimidin-4-yl)amino)-4,4-dimethylpentanoate, 6a, (14.1 g, 48.6 mmol) and K3PO4 (30.9 g, 146 mmol) was purged with nitrogen for 0.75 h. XPhos (2.8 g, 5.8 mmol) and Pd2(dba)3 (1.1 g, 1.2 mmol) were added and the reaction mixture was stirred at 115° C. in a sealed tube for 2 h. The reaction mixture was cooled and the aqueous phase was removed. The organic phase was filtered through a pad of Celite and the mixture was concentrated to dryness. The residue was purified on silica gel (EA/Hex) to provide the desired product, 8a, (23.2 g): LCMS Gradient 10-90%, 0.1% formic acid, 5 min, C18/ACN, RT=2.18 minutes (M+H) 245.28.

후처리

  1. temperatureThe reaction mixture was cooled
  2. customthe aqueous phase was removed
  3. filtrationThe organic phase was filtered through a pad of Celite
  4. concentrationthe mixture was concentrated to dryness
  5. customThe residue was purified on silica gel (EA/Hex)

출처 및 근거

ORD 기록
ord-bb683614ef9e429d9cbdb471afd7169a
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394302B2

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