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Water → 2-(6-(1-benzyl-1H-pyrazol-4-yl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-6,6-dimethyl-6,7-dihydrothiazolo[5,4-c]pyridin-4(5H)-one

HRID 885960
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HRID 885960 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:11]3[S:12][C:13]4[CH2:14]C(C)(C)N[C:17](=O)[C:18]=4[N:19]=3)[C:6]=2[CH:23]=1.[CH2:24]([N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+].[OH2:51]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.CCOC(C)=O>[CH2:24]([N:31]1[CH:35]=[C:34]([C:2]2[CH:3]=[CH:4][C:5]3[O:10][CH2:9][CH2:8][N:7]([C:11]4[S:12][C:13]5[C:14](=[O:51])[NH:7][C:6]([CH3:23])([CH3:5])[CH2:17][C:18]=5[N:19]=4)[C:6]=3[CH:23]=2)[CH:33]=[N:32]1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
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참가 물질

8

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27347711-Benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 685972362-(6-Bromo-2,3-dihydrobenzo[1,4]oxazin-4-yl)-6,6-dimethyl-6,7-dihydro-[1,3]thiazolo[5,4-d]pyridin-4(5h)-one

생성물 1

HCID 445807222-(6-(1-benzyl-1H-pyrazol-4-yl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-6,6-dimethyl-6,7-dihydrothiazolo[5,4-c]pyridin-4(5H)-one
수율 68%

시약·촉매·용매 3

HCID 74236Tetrabutylammonium Bromide촉매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

A stirred solution of Example 39 (0.051 g, 0.129 mmol), 1-benzyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.049 g, 0.173 mmol), K2CO3 (0.054 g, 0.388 mmol), tetra-n-butylammonium bromide (0.124 g, 0.385 mmol), tetrakis-(triphenylphosphine)palladium(0) (0.010 g, 0.009 mmol) and H2O (0.5 mL) in THF (1 mL) was heated to 125° C. under microwave irradiation for 1 h. The reaction mixture was diluted with EtOAc and washed with water and brine. The organic fractions were dried (MgSO4), filtered and concentrated in vacuo. The crude material was triturated with Et2O to give the title compound (0.041 g, 68%) as a beige solid. δH (CDCl3) 8.03 (1H, d, J 1.9 Hz), 7.78 (1H, s), 7.60 (1H, s), 7.40-7.25 (5H, m), 7.18 (1H, dd, J 8.5 and J 2.1 Hz), 6.96 (1H, d, J 8.3 Hz), 5.37 (2H, s), 5.26 (1H, br. s), 4.38-4.32 (2H, m), 4.22-4.16 (2H, m), 2.89 (2H, s), 1.42 (6H, s). LCMS (ES+) 472.0 (M+H)+, RT 3.53 minutes (Method 1).

후처리

  1. washwashed with water and brine
  2. dry with materialThe organic fractions were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude material was triturated with Et2O

출처 및 근거

ORD 기록
ord-08c3178ca4bb4603b45f155768738a38
출처 데이터셋
uspto-grants-2012_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08242116B2

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