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Sodium Carbonate → (3R)-tert-butyl 3-(6-(5-(2-chloropyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate

HRID 1529369
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HRID 1529369 반응식
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:15]2[C:10](=[CH:11][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:13][CH:14]=2)[C:9]([C:25]2[N:30]=[C:29]([O:31][C@@H:32]3[CH2:37][CH2:36][CH2:35][N:34]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:33]3)[CH:28]=[N:27][CH:26]=2)=[N:8]1.[Cl:45][C:46]1[N:51]=[C:50](Cl)[CH:49]=[CH:48][N:47]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[Cl:45][C:46]1[N:51]=[C:50]([C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[N:7]([CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[N:8]=[C:9]3[C:25]2[N:30]=[C:29]([O:31][C@@H:32]3[CH2:37][CH2:36][CH2:35][N:34]([C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])[CH2:33]3)[CH:28]=[N:27][CH:26]=2)[CH:49]=[CH:48][N:47]=1
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참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 775312,4-DichloropyrimidineHCID 86709761(3R)-tert-butyl 3-(6-(1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate

생성물 1

HCID 86709777(3R)-tert-butyl 3-(6-(5-(2-chloropyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate수율 86%

시약·촉매·용매

2
HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

A glass microwave reaction vessel was charged with (3R)-tert-butyl 3-(6-(1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate (600 mg, 0.99 mmol), 2,4-dichloropyrimidine (192 mg, 1.29 mmol, Fluka) and Pd(PPh3)4 (57 mg, 0.050 mmol). The tube was sealed and evacuated under vacuum and back-filled with N2 three times. 2 M Na2CO3 (2.48 mL, 4.95 mmol) and dioxane (5 mL) were added. The reaction was stirred and heated in at 100° C. for 3 h. After cooling to RT, the organic layer was separated and dried over anhydrous Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography, eluting with a gradient of 0-60% EtOAc in hexanes, to provide (3R)-tert-butyl 3-(6-(5-(2-chloropyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate (505 mg, 0.85 mmol, 86% yield) as a pale yellow solid. MS (ESI, pos. ion) m/z: 592.1 (M+1).

후처리

  1. customA glass microwave reaction vessel
  2. customThe tube was sealed
  3. customevacuated under vacuum
  4. additionback-filled with N2 three times
  5. temperatureAfter cooling to RT
  6. customthe organic layer was separated
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude was purified by silica gel chromatography
  11. washeluting with a gradient of 0-60% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-27dc4ab8bfb244ffb93a6352a8307db4
출처 데이터셋
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09090593B2

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