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Water → 6,6-Dimethyl-2-(6-{1-[2-(morpholin-4-yl)ethyl]-1h-pyrazol-4-yl}-2,3-dihydrobenzo[1,4]oxazin-4-yl)-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

HRID 885959
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반응식

HRID 885959 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.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[N:34][N:35]([CH2:37][CH2:38][N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)[CH:36]=2)O1.C([O-])([O-])=O.[K+].[K+].[OH2:52]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1.CCOC(C)=O.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>[CH3:5][C:6]1([CH3:23])[NH:7][C:14](=[O:52])[C:13]2[S:12][C:11]([N:7]3[C:6]4[CH:23]=[C:2]([C:32]5[CH:33]=[N:34][N:35]([CH2:37][CH2:38][N:39]6[CH2:40][CH2:41][O:42][CH2:43][CH2:44]6)[CH:36]=5)[CH:3]=[CH:4][C:5]=4[O:10][CH2:9][CH2:8]3)=[N:19][C:18]=2[CH2:17]1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 177499241-(2-Morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 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 671876196,6-Dimethyl-2-(6-{1-[2-(morpholin-4-yl)ethyl]-1h-pyrazol-4-yl}-2,3-dihydrobenzo[1,4]oxazin-4-yl)-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one
수율 41%

시약·촉매·용매 4

HCID 74236Tetrabutylammonium Bromide촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

A stirred solution of Example 39 (0.1 g, 0.326 mmol), 4-{2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazol-1-yl]ethyl}morpholine (0.051 g, 0.165 mmol), K2CO3 (0.054 g, 0.395 mmol), tetra-n-butylammonium bromide (0.122 g, 0.377 mmol), tetrakis(triphenylphosphine)palladium(0) (0.007 g, 0.006 mmol) and H2O (0.5 mL) in THF (1 mL) was heated at 125° C. in a sealed vessel for 2.5 days. After cooling to r.t. the reaction mixture was diluted with EtOAc and washed with water and brine. The organic fraction was dried (MgSO4), filtered and concentrated in vacuo. Purification by column chromatography (SiO2, 0-100% [9:1 EtOAc/MeOH]/heptane) followed by trituration with Et2O gave the title compound (0.026 g, 41%) as a white solid. δH (CDCl3) 8.00 (1H, d, J 2.1 Hz), 7.72 (1H, s), 7.68 (1H, s), 7.20 (1H, dd, J 8.5 and J 2.1 Hz), 6.97 (1H, d, J 8.5 Hz), 5.27 (1H, br. s), 4.39-4.26 (4H, m), 4.25-4.19 (2H, m), 3.78-3.69 (4H, m), 2.95-2.83 (4H, m), 2.61-2.49 (4H, m), 1.42 (6H, s). LCMS (ES+) 495.5 (M+H)+, RT 2.04 minutes (Method 1).

후처리

  1. washwashed with water and brine
  2. dry with materialThe organic fraction was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by column chromatography (SiO2, 0-100% [9:1 EtOAc/MeOH]/heptane)

출처 및 근거

ORD 기록
ord-f48a7cfd31564d4bb715fd711177075c
출처 데이터셋
uspto-grants-2012_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08242116B2

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