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Potassium Acetate → tert-butyl 4-((1R)-1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate

HRID 1812267
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HRID 1812267 반응식
Cl[C:2]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][N:28]([C@@H:31]([C:33]2[CH:34]=[C:35](B(O)O)[C:36]([F:39])=[N:37][CH:38]=2)[CH3:32])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C([O-])(=O)C.[K+]>O1CCOCC1.ClCCl.O.[Cl-].[Na+].O>[F:39][C:36]1[N:37]=[CH:38][C:33]([C@H:31]([N:28]2[CH2:27][CH2:26][N:25]([C:23]([O:22][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:24])[CH2:30][CH2:29]2)[CH3:32])=[CH:34][C:35]=1[C:2]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1
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참가 물질

8

반응물 3

HCID 517044Potassium AcetateHCID 595482686-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 66600472(R)-5-(1-(4-(tert-butoxycarbonyl)piperazin-1-yl)ethyl)-2-fluoropyridin-3-ylboronic acid

생성물 1

HCID 68518749tert-butyl 4-((1R)-1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate수율 77%

시약·촉매·용매 4

HCID 962
Water
용매
2회
HCID 6344Dichloromethane용매
HCID 312751,4-Dioxane용매
HCID 57417360Sodium chloride; water용매

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온도
120 °C

실험 절차

A glass microwave reaction vessel was charged with 6-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (0.250 g, 0.989 mmol) and (R)-5-(1-(4-(tert-butoxycarbonyl)piperazin-1-yl)ethyl)-2-fluoropyridin-3-ylboronic acid (0.489 g, 1.385 mmol) in dioxane (3 mL). Then A-Phos (0.070 g, 0.099 mmol), potassium acetate (0.291 g, 2.97 mmol) and water (0.5 mL) were added into the reaction mixture. The reaction mixture was stirred and heated in a CEM Explorer Microwave at 120° C. for 10 min (120 watts, Powermax feature on). The mixture was diluted with dichloromethane (10 mL), water (10 mL) and brine solution (5 mL). The organic layer was collected by extracting with dichloromethane (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to give the crude material as a tan oil. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica-gel column (40 g) eluting with 100% ethyl acetate to give tert-butyl 4-((1R)-1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate (0.400 g, 0.761 mmol, 77% yield) as a light-yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.20-8.29 (m, 3H) 5.78 (dd, J=10.37, 2.35 Hz, 1H) 3.76 (s, 1H) 3.55 (d, J=6.65 Hz, 1H) 3.34 (s, 5H) 2.82 (s, 3H) 2.33 (d, J=5.09 Hz, 5H) 1.95-2.13 (m, 3H) 1.56-1.81 (m, 5H) 1.33-1.40 (m, 9H). m/z (ESI, +ve ion) 526.2 (M+H)+.

후처리

  1. customA glass microwave reaction vessel
  2. customThe organic layer was collected
  3. extractionby extracting with dichloromethane (3×10 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give the crude material as a tan oil
  8. custompurified by chromatography through a silica-gel column (40 g)
  9. washeluting with 100% ethyl acetate

출처 및 근거

ORD 기록
ord-1b003636f5f04b379bdc862437b854ac
출처 데이터셋
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08362241B2

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