4-Aminobenzonitrile → tert-butyl ((S)-1-(((1S,3R)-3-((2-((4-cyanophenyl)amino)-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284790ノート

反応式

HRID 2284790 の反応式
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]#[C:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][C@H:14]([NH:18][C:19](=[O:31])[C@@H:20]([N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH3:21])[CH2:13]2)=[CH:4][N:3]=1.[NH2:32][C:33]1[CH:40]=[CH:39][C:36]([C:37]#[N:38])=[CH:35][CH:34]=1.[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)([O-])O.[Na+]>CN1CCCC1=O.C(OCC)(=O)C>[C:37]([C:36]1[CH:39]=[CH:40][C:33]([NH:32][C:2]2[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]#[C:11][C@@H:12]3[CH2:17][CH2:16][CH2:15][C@H:14]([NH:18][C:19](=[O:31])[C@@H:20]([N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:28])[CH3:26])[CH3:21])[CH2:13]3)=[CH:4][N:3]=2)=[CH:34][CH:35]=1)#[N:38]

参加物

7

反応物 4

HCID 133964-AminobenzonitrileHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 516892Sodium BicarbonateHCID 90052347tert-butyl ((S)-1-(((1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

生成物 1

HCID 90052364tert-butyl ((S)-1-(((1S,3R)-3-((2-((4-cyanophenyl)amino)-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
60 °C

実験手順

To a solution of tert-butyl ((S)-1-(((1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (Q4, 32 mg) in N-methylpyrrolidone (0.5 mL), 4-aminobenzonitrile (42 mg) and (1S)-(+)-10-camphorsulfonic acid (81 mg) were added at room temperature, and the mixture was stirred at 60° C. for 7 hours and 30 minutes. The reaction mixture was cooled to room temperature, and then saturated aqueous sodium hydrogencarbonate and ethyl acetate were added to the reaction mixture. The organic layer was separated, washed successively with saturated aqueous sodium hydrogencarbonate, water and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 88 to 25% hexane in ethyl acetate) to obtain tert-butyl ((S)-1-(((1S,3R)-3-((2-((4-cyanophenyl)amino)-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (Q5, 11 mg).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. washwashed successively with saturated aqueous sodium hydrogencarbonate, water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent, 88 to 25% hexane in ethyl acetate)

出典と根拠

ORDレコード
ord-fffb83e3de8143bfb90ae90163702cef
出典データセット
uspto-grants-2015_09
特許番号
US09145415B2

反応ノート

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