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Potassium Iodide → tert-Butyl 3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl}azetidine-1-carboxylate

HRID 1499804
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HRID 1499804 반응식
[CH3:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+].[Cl:20][C:21]1[C:22]([F:44])=[C:23]([CH:33]2[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:34]2)[C:24]([O:30][CH2:31][CH3:32])=[C:25]([CH:27](Cl)[CH3:28])[CH:26]=1>CN(C=O)C>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:27]([C:25]3[C:24]([O:30][CH2:31][CH3:32])=[C:23]([CH:33]4[CH2:34][N:35]([C:37]([O:39][C:40]([CH3:42])([CH3:41])[CH3:43])=[O:38])[CH2:36]4)[C:22]([F:44])=[C:21]([Cl:20])[CH:26]=3)[CH3:28])[N:3]=[C:2]([CH3:1])[C:10]=12
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참가 물질

6

반응물 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 86677726HCID 86677726, 화합물HCID 178434474HCID 178434474, 화합물

생성물 1

HCID 86677728tert-Butyl 3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-ethoxy-6-fluorophenyl}azetidine-1-carboxylate수율 63.5%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

To a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1.10 g, 7.37 mmol), cesium carbonate (3.2 g, 10 mmol) and potassium iodide (111 mg, 0.670 mmol) in DMF (20 mL) was added tert-butyl 3-[3-chloro-5-(1-chloroethyl)-6-ethoxy-2-fluorophenyl]azetidine-1-carboxylate (2.63 g, 6.70 mmol) and the mixture was stirred at 90° C. for 3 h. The solvent was removed in vacuo. The residue was diluted with ethyl acetate and water. Aqueous layer was extracted with ethyl acetate twice. The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel column (eluting with 100% ethyl acetate) to give the desired product as a foam (2.15 g, 63%). LCMS calculated for C24H31ClFN6O3 (M+H)+: m/z=505.2; Found: 505.2.

후처리

  1. customThe solvent was removed in vacuo
  2. additionThe residue was diluted with ethyl acetate and water
  3. extractionAqueous layer was extracted with ethyl acetate twice
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel column (eluting with 100% ethyl acetate)

출처 및 근거

ORD 기록
ord-c73606a6816b499f94efad4a59f21ac0
출처 데이터셋
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09199982B2

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