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Sodium hydride → 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile

HRID 1499738
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HRID 1499738 반응식
[H-].[Na+].[CH3:3][C:4]1[C:12]2[C:7](=[N:8][CH:9]=[N:10][C:11]=2[NH2:13])[NH:6][N:5]=1.[Br:14][C:15]1[C:22]([O:23][CH2:24][CH3:25])=[C:21]([CH:26](Cl)[CH3:27])[CH:20]=[C:19]([Cl:29])[C:16]=1[C:17]#[N:18]>CN(C)C=O.C(Cl)Cl>[NH2:13][C:11]1[N:10]=[CH:9][N:8]=[C:7]2[N:6]([CH:26]([C:21]3[CH:20]=[C:19]([Cl:29])[C:16]([C:17]#[N:18])=[C:15]([Br:14])[C:22]=3[O:23][CH2:24][CH3:25])[CH3:27])[N:5]=[C:4]([CH3:3])[C:12]=12
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참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 866776672-Bromo-6-chloro-4-(1-chloroethyl)-3-ethoxybenzonitrileHCID 178434474HCID 178434474, 화합물

생성물 1

HCID 866776684-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile수율 60%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회
HCID 6344Dichloromethane용매

실험 절차

Sodium hydride (16 mg, 0.41 mmol) was added to a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (33 mg, 0.22 mmol) in N,N-dimethylformamide (3 mL, 40 mmol) and was stirred for 10 minutes. 2-bromo-6-chloro-4-(1-chloroethyl)-3-ethoxybenzonitrile (60 mg, 0.2 mmol) in N,N-dimethylformamide (2 mL) was added and the reaction was stirred at 50° C. overnight. The mixture was diluted with methylene chloride, washed with sat'd NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The product was purified by flash column chromatography eluting with CH2Cl2/MeOH 0-10%, to give 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-bromo-6-chloro-3-ethoxybenzonitrile (0.05 gm, 60%) as a solid, LCMS calculated for C17H16BrClN6O (M+H)+: m/z=437.0, 435.0; found: 436.9, 434.7.

후처리

  1. stirringthe reaction was stirred at 50° C. overnight
  2. washwashed with sat'd NaHCO3, water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe product was purified by flash column chromatography
  7. washeluting with CH2Cl2/MeOH 0-10%

출처 및 근거

ORD 기록
ord-1c508c27351745558d130b738bb4ac28
출처 데이터셋
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09199982B2

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