Cesium carbonate → 5-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-cyano-2-methoxyphenyl}-N,N-dimethylpyridine-2-carboxamide

HRID 1499899노트

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HRID 1499899 반응식
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[N:14][C:15]=2[NH2:17])[NH:10][N:9]=1.[Cl:18][C:19]1[C:20]([C:41]#[N:42])=[C:21]([C:30]2[CH:31]=[CH:32][C:33]([C:36]([N:38]([CH3:40])[CH3:39])=[O:37])=[N:34][CH:35]=2)[C:22]([O:28][CH3:29])=[C:23]([CH:25](Cl)[CH3:26])[CH:24]=1>CN(C)C=O.CCOC(C)=O>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:25]([C:23]3[C:22]([O:28][CH3:29])=[C:21]([C:30]4[CH:31]=[CH:32][C:33]([C:36]([N:38]([CH3:39])[CH3:40])=[O:37])=[N:34][CH:35]=4)[C:20]([C:41]#[N:42])=[C:19]([Cl:18])[CH:24]=3)[CH3:26])[N:9]=[C:8]([CH3:7])[C:16]=12

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 866778215-[3-chloro-5-(1-chloroethyl)-2-cyano-6-methoxyphenyl]-N,N-dimethylpyridine-2-carboxamideHCID 178434474HCID 178434474, 화합물

생성물 1

HCID 866778225-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-cyano-2-methoxyphenyl}-N,N-dimethylpyridine-2-carboxamide수율 84.9%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

Cesium carbonate (3000 mg, 10 mmol) was added to a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1100 mg, 7.1 mmol) and 5-[3-chloro-5-(1-chloroethyl)-2-cyano-6-methoxyphenyl]-N,N-dimethylpyridine-2-carboxamide (1.8 g, 4.8 mmol) in N,N-dimethylformamide (50 mL). The reaction was stirred at 80° C. for 3 hrs and was allowed to cool to room temperature. The reaction was diluted with EtOAc, washed with water, brine, dried over Na2SO4, filtered and concentrated to give the crude product. This was purified by FCC on silica gel eluting (hexanes/10% EtOH in EtOAc, 0-100%) gradient to give the title compound as light yellow oil (2.0 g, 80%). LCMS calculated for C24H24ClN8O2 (M+H)+: m/z=491.1; found: 491.2. NMR (400 MHz, CD3OD) δ 8.74 (d, J=1.4 Hz, 1H), 8.15 (d, J=2.2 Hz, 1H), 8.13 (s, 1H), 7.77 (d, J=8.1 Hz, 1H), 7.74 (s, 1H), 6.43 (q, J=7.0 Hz, 1H), 3.32 (s, 3H), 3.16 (s, 3H), 3.07 (s, 3H), 2.64 (s, 3H), 1.89 (d, J=7.1 Hz, 3H).

후처리

  1. temperatureto cool to room temperature
  2. washwashed with water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customThis was purified by FCC on silica gel eluting (hexanes/10% EtOH in EtOAc, 0-100%) gradient

출처 및 근거

ORD 기록
ord-6b0b39951278498e94a402c05b61c23c
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09199982B2

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