Cesium carbonate → tert-butyl (1S,2R)-2-(6-cyano-5-(5-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-2-ylamino)pyridin-3-ylamino)cyclohexylcarbamate

HRID 1504889노트

반응식

HRID 1504889 반응식
[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([CH3:13])([OH:12])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1.Br[C:15]1[CH:16]=[C:17]([NH:23][C@@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]2[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH:18]=[N:19][C:20]=1[C:21]#[N:22].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(OCC)(=O)C.C(=O)(O)[O-].[Na+].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]>[C:21]([C:20]1[N:19]=[CH:18][C:17]([NH:23][C@@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]2[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[CH:16][C:15]=1[NH:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8]([OH:12])([CH3:13])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1)#[N:22]

참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86716545tert-butyl (1S,2R)-2-(5-bromo-6-cyanopyridin-3-ylamino)cyclohexylcarbamateHCID 867317622-Amino-5-methyl-5,6,7,8-tetrahydroquinolin-5-ol

생성물 1

HCID 86731763tert-butyl (1S,2R)-2-(6-cyano-5-(5-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-2-ylamino)pyridin-3-ylamino)cyclohexylcarbamate

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
80 °C

실험 절차

A mixture of 2-amino-5-methyl-5,6,7,8-tetrahydroquinolin-5-ol (45.4 mg, 0.255 mmol), tert-butyl (1S,2R)-2-(5-bromo-6-cyanopyridin-3-ylamino)cyclohexylcarbamate (PrepEx 1.1) (111 mg, 0.280 mmol), Xantphos (15 mg, 0.025 mmol), tris(dibenzylideneacetone)dipalladium(0) (12 mg, 0.013 mmol), and cesium carbonate (207 mg, 0.637 mmol) in 1,4-dioxane (10 ml) under an argon atmosphere was heated at 80° C. in an oil bath for 2.25 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (30 mL) and saturated aqueous sodium bicarbonate solution (10 mL). The layers were separated, and the organic layer was washed with brine (10 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (1-5% methanol/dichloromethane, linear gradient) to give tert-butyl (1S,2R)-2-(6-cyano-5-(5-hydroxy-5-methyl-5,6,7,8-tetrahydroquinolin-2-ylamino)pyridin-3-ylamino)cyclohexylcarbamate. MS ESI calc'd. for C27H37N6O3 [M+H]+ 493. found 493.

후처리

  1. temperatureAfter cooling to room temperature
  2. customThe layers were separated
  3. washthe organic layer was washed with brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on silica gel (1-5% methanol/dichloromethane, linear gradient)

출처 및 근거

ORD 기록
ord-81b74b8978a74af688b117c9de8883e0
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216173B2

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