Water → methyl (3R)-3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-4,4-dimethylpentanoate

HRID 1055037ノート

反応式

HRID 1055037 の反応式
[Cl-].[CH3:2][O:3][C:4](=[O:12])[CH2:5][C@@H:6]([NH3+:11])[C:7]([CH3:10])([CH3:9])[CH3:8].[Cl:13][C:14]1[N:19]=[C:18](Cl)[C:17]([F:21])=[CH:16][N:15]=1.C(N(CC)CC)C.O>O1CCCC1.CCO.ClCCl>[Cl:13][C:14]1[N:19]=[C:18]([NH:11][C@@H:6]([C:7]([CH3:8])([CH3:9])[CH3:10])[CH2:5][C:4]([O:3][CH3:2])=[O:12])[C:17]([F:21])=[CH:16][N:15]=1

参加物

8

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 86714730(R)-1-methoxy-4,4-dimethyl-1-oxopentan-3-aminium chloride2 回

生成物 1

HCID 86714731methyl (3R)-3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-4,4-dimethylpentanoate

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
55 °C

実験手順

(R)-1-methoxy-4,4-dimethyl-1-oxopentan-3-aminium chloride, 5a, (37 g, 189 mmol) was dissolved in a mixture of tetrahydrofuran (667 mL) and EtOH (74 mL). The solution was cooled in an ice bath. 2,4-dichloro-5-fluoro-pyrimidine (35 g, 208 mmol) was added, followed by the dropwise addition of triethylamine (85 mL, 606 mmol). The reaction mixture was heated at 55° C. for 17 h. The reaction mixture was then cooled to room temperature after which water (625 mL) and dichloromethane (625 mL) were added. The phases were separated and the aqueous layer was washed with dichloromethane (625 mL). The organic layers were combined and washed with brine. The solvents were removed and the residue was purified on silica gel (EtOAc/Hexanes): LCMS Gradient 10-90%, 0.1% formic acid, 5 min, C18/ACN, RT=3.10 minutes (M+H) 291.02.

後処理

  1. temperatureThe solution was cooled in an ice bath
  2. additionwere added
  3. customThe phases were separated
  4. washthe aqueous layer was washed with dichloromethane (625 mL)
  5. washwashed with brine
  6. customThe solvents were removed
  7. customthe residue was purified on silica gel (EtOAc/Hexanes)
  8. customLCMS Gradient 10-90%, 0.1% formic acid, 5 min

出典と根拠

ORDレコード
ord-d25a1ae188d04b3eada7f5fb82f57f76
出典データセット
uspto-grants-2016_07
特許番号
US09394302B2

反応ノート

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