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

HRID 2171832노트

반응식

HRID 2171832 반응식
[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

참가 물질

8

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 86714730(R)-1-methoxy-4,4-dimethyl-1-oxopentan-3-aminium chloride2회

생성물 1

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

시약·촉매·용매 3

HCID 702Ethanol용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
55 °C

실험 절차

(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.

후처리

  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

출처 및 근거

ORD 기록
ord-bfb7b7f7271a42b5884edcf7921a1431
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09051319B2

반응 노트

불러오는 중…