Diisopropylethylamine → (1R,3S)-3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)cyclohexanecarbonitrile

HRID 527035

반응식

HRID 527035 반응식
[C:1]([C@@H:3]1[CH2:8][CH2:7][CH2:6][C@H:5]([NH:9][C:10](=O)OCC2C=CC=CC=2)[CH2:4]1)#[N:2].CCN(C(C)C)C(C)C.[Cl:29][C:30]1[CH:31]=[C:32]2[C:38]([C:39]3[N:44]=C(S(C)=O)[C:42]([F:48])=[CH:41][N:40]=3)=[CH:37][N:36]([S:49]([C:52]3[CH:58]=[CH:57][C:55]([CH3:56])=[CH:54][CH:53]=3)(=[O:51])=[O:50])[C:33]2=[N:34][CH:35]=1>C1COCC1.[OH-].[OH-].[Pd+2]>[Cl:29][C:30]1[CH:31]=[C:32]2[C:38]([C:39]3[N:44]=[C:10]([NH:9][C@H:5]4[CH2:6][CH2:7][CH2:8][C@@H:3]([C:1]#[N:2])[CH2:4]4)[C:42]([F:48])=[CH:41][N:40]=3)=[CH:37][N:36]([S:49]([C:52]3[CH:53]=[CH:54][C:55]([CH3:56])=[CH:57][CH:58]=3)(=[O:51])=[O:50])[C:33]2=[N:34][CH:35]=1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 23584440benzyl N-[(1S,3R)-3-cyanocyclohexyl]carbamateHCID 672853215-Chloro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridine

생성물 1

HCID 68007570(1R,3S)-3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)cyclohexanecarbonitrile

시약·촉매·용매 2

HCID 9942167Palladium hydroxide촉매HCID 8028Tetrahydrofuran용매

반응 조건

온도
45 °C

실험 절차

Benzyl N-[(1S,3R)-3-cyanocyclohexyl]carbamate (0.26 g, 1.02 mmol) was dissolved in THF (15 mL) and treated with 0.13 g of 20% Pearlman's catalyst (50% wet by weight). The suspension was degassed with hydrogen for 2 min then placed under static hydrogen atmosphere. After 135 min, TLC showed no remaining starting material. The suspension was filtered through celite, washed with THF and degassed with nitrogen followed by the addition of iPr2NEt (0.21 mL, 1.23 mmol) and 5-chloro-3-(5-fluoro-4-(methylsulfinyl)pyrimidin-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine, 1a, (0.48 g, 1.02 mmol). The mixture was allowed to stir overnight at 45° C. then concentrated to dryness, absorbed on silica-gel and purified by silica gel chromatography using 0-60% EtOAc/hexanes gradient to afford 293 mg of a white solid.

후처리

  1. customThe suspension was degassed with hydrogen for 2 min
  2. filtrationThe suspension was filtered through celite
  3. washwashed with THF
  4. customdegassed with nitrogen
  5. concentrationthen concentrated to dryness
  6. customabsorbed on silica-gel
  7. custompurified by silica gel chromatography

출처 및 근거

ORD 기록
ord-5770fda548b64e78ac99773e01c07234
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345708B2

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