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

HRID 1499750
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HRID 1499750 반응식
[Cl:1][C:2]1[C:3]([F:24])=[C:4]([CH:13]2[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]2)[C:5]([O:11][CH3:12])=[C:6]([CH:8](Cl)[CH3:9])[CH:7]=1.[I:25][C:26]1[C:34]2[C:29](=[N:30][CH:31]=[N:32][C:33]=2[NH2:35])[NH:28][N:27]=1.[I-].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.CCOC(C)=O>[NH2:35][C:33]1[N:32]=[CH:31][N:30]=[C:29]2[N:28]([CH:8]([C:6]3[C:5]([O:11][CH3:12])=[C:4]([CH:13]4[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]4)[C:3]([F:24])=[C:2]([Cl:1])[CH:7]=3)[CH3:9])[N:27]=[C:26]([I:25])[C:34]=12
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참가 물질

8

반응물 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 86666861Tert-butyl 3-(3-chloro-5-(1-chloroethyl)-2-fluoro-6-methoxyphenyl)azetidine-1-carboxylate2회HCID 178508725HCID 178508725, 화합물

생성물 1

HCID 86677679tert-Butyl 3-{3-[1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-fluoro-2-methoxyphenyl}azetidine-1-carboxylate
수율 45.6%

시약·촉매·용매 3

HCID 962Water용매2회HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매2회

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온도
140 °C

실험 절차

To a mixture of tert-butyl 3-[3-chloro-5-(1-chloroethyl)-2-fluoro-6-methoxyphenyl]azetidine-1-carboxylate (0.77 g, 2.0 mmol, racemic intermediate from Example 13, Step 6), 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.58 g, 2.2 mmol) in N,N-dimethylformamide (6.9 mL) was added potassium iodide (34 mg, 0.20 mmol) and cesium carbonate (0.99 g, 3.0 mmol). The resulting mixture was heated at 140° C. and stirred for 3 h. After cooling, the clear solution was taken into water and ethyl acetate (EtOAc). The solid was diluted with water and EtOAc, and stirred until dissolved. The organic layers were combined, concentrated and purified on silica gel (eluting with 0 to 100% EtOAc in hexanes) to give the desired product (0.55 g, 45%). LCMS calculated for C22H26ClFN6O3 (M+H)+: m/z=603.1; Found: 602.9.

후처리

  1. temperatureAfter cooling
  2. stirringstirred
  3. dissolutionuntil dissolved
  4. concentrationconcentrated
  5. custompurified on silica gel (eluting with 0 to 100% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-89dc369a2df440ecbfeaea14594dd853
출처 데이터셋
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09199982B2

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