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 1504889ノート

反応式

HRID 1504889 の反応式
[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]

参加物

9

反応物 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

生成物 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

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-81b74b8978a74af688b117c9de8883e0
出典データセット
uspto-grants-2015_12
特許番号
US09216173B2

反応ノート

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