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

HRID 2284789ノート

反応式

HRID 2284789 の反応式
[C:1]([N:8]([CH3:14])[C@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Cl:15][C:16]1[N:21]=[C:20]([O:22][CH3:23])[C:19]([C:24]#[C:25][C@@H:26]2[CH2:31][CH2:30][CH2:29][C@H:28]([NH2:32])[CH2:27]2)=[CH:18][N:17]=1.Cl.C(=O)([O-])O.[Na+]>CN(C)C=O.CN1CCOCC1.ClC(OCC(C)C)=O.C(OCC)(=O)C>[Cl:15][C:16]1[N:21]=[C:20]([O:22][CH3:23])[C:19]([C:24]#[C:25][C@@H:26]2[CH2:31][CH2:30][CH2:29][C@H:28]([NH:32][C:11](=[O:13])[C@@H:9]([N:8]([CH3:14])[C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])[CH3:10])[CH2:27]2)=[CH:18][N:17]=1

参加物

9

反応物 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 90052507(1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexaneamine

生成物 1

HCID 90052347tert-butyl ((S)-1-(((1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide溶媒2 回HCID 79724-Methylmorpholine溶媒HCID 8857Ethyl Acetate溶媒HCID 62365Isobutyl chloroformate溶媒

実験手順

To a solution of N-Boc-N-methyl-L-alanine (195 mg) in N,N-dimethylformamide (2.5 mL), N-methylmorpholine (246 μL) and isobutyl chloroformate (105 μL) were added under ice cooling, and the mixture was stirred at the same temperature for 2 minutes. To the reaction mixture, a solution of (1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexaneamine (Q3) hydrochloride in N,N-dimethylformamide (2 mL) was added under ice cooling, and the mixture was stirred at the same temperature for 1 hour and 30 minutes. To the reaction mixture, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, washed successively with water, saturated aqueous sodium hydrogencarbonate 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 40% hexane in ethyl acetate) to obtain tert-butyl ((S)-1-(((1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (Q4, 120 mg).

後処理

  1. stirringthe mixture was stirred at the same temperature for 1 hour and 30 minutes
  2. customThe organic layer was separated
  3. washwashed successively with water, saturated aqueous sodium hydrogencarbonate 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 40% hexane in ethyl acetate)

出典と根拠

ORDレコード
ord-d2f40397b4084f23b0e1da5b2fdddefd
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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