Triethylamine → (S)-2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutan-1-ol

HRID 1055041노트

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HRID 1055041 반응식
[NH2:1][C@@H:2]([C:5]([CH3:8])([CH3:7])[CH3:6])[CH2:3][OH:4].[Cl:9][C:10]1[N:15]=[C:14](Cl)[C:13]([F:17])=[CH:12][N:11]=1.C(N(CC)CC)C.[NH4+].[Cl-]>CN(C=O)C>[Cl:9][C:10]1[N:15]=[C:14]([NH:1][C@@H:2]([C:5]([CH3:8])([CH3:7])[CH3:6])[CH2:3][OH:4])[C:13]([F:17])=[CH:12][N:11]=1

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 2734079(2S)-2-Amino-3,3-dimethyl-1-butanol

생성물 1

HCID 86714732(S)-2-((2-chloro-5-fluoropyrimidin-4-yl)amino)-3,3-dimethylbutan-1-ol수율 63.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a mixture of (2S)-2-amino-3,3-dimethyl-butan-1-ol (5.0 g, 42.7 mmol) and 2,4-dichloro-5-fluoro-pyrimidine (5.7 g, 42.7 mmol) in DMF (50 mL) was added triethylamine (7.1 mL, 51.2 mmol). After 90 minutes, the reaction was diluted into aqueous saturated NH4Cl solution and extracted twice with EtOAc. The combined organic phases were washed twice with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (0-10% MeOH/CH2Cl2 gradient) to afford 6.7 g of the desired product, 1, as a sticky solid: LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=2.48 minutes (M+H) 248.32.

후처리

  1. extractionextracted twice with EtOAc
  2. washThe combined organic phases were washed twice with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (0-10% MeOH/CH2Cl2 gradient)

출처 및 근거

ORD 기록
ord-8ec5419a5a3c468d8de4f303281bf40e
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394302B2

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