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Sodium Carbonate → 2-Methyl-2-(4-((2-(2-methylbenzofuran-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide

HRID 1945730
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HRID 1945730 반응식
Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([C:18]([CH3:23])([CH3:22])[C:19]([NH2:21])=[O:20])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:38]2[C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=3[O:40][C:39]=2[CH3:47])O1.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(=O)C.[K+]>C(#N)C.O.CCOC(C)=O>[CH3:22][C:18]([N:15]1[CH2:16][CH2:17][N:12]([CH2:11][C:9]2[S:10][C:5]3[C:4]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[N:3][C:2]([C:38]4[C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=5[O:40][C:39]=4[CH3:47])=[N:7][C:6]=3[CH:8]=2)[CH2:13][CH2:14]1)([CH3:23])[C:19]([NH2:21])=[O:20]
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참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 574940122-(4-((2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamideHCID 673417654,4,5,5-Tetramethyl-2-(2-methylbenzofuran-3-yl)-1,3,2-dioxaborolane

생성물 1

HCID 596058752-Methyl-2-(4-((2-(2-methylbenzofuran-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)propanamide
수율 30.7%

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

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온도
140 °C

실험 절차

To a degassed suspension of 2-(4-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-methylpropanamide (90.0 mg 0.205 mmol), 4,4,5,5-tetramethyl-2-(2-methylbenzofuran-3-yl)-1,3,2-dioxaborolane (120 mg, 0.46 mmol) in acetonitrile (2 mL) was added 2 M aqueous solution of sodium carbonate (0.20 mL) and 1M aqueous solution of potassium acetate (0.2 mL). The mixture was then heated in a microwave at 140° C. for 30 minutes. The reaction mixture was diluted with water and EtOAc. The aqueous layer was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by RP-HPLC to give 140 (33.6 mg, 30.6%). LCMS: M+H+=535.2. 1H-NMR (400 MHz, DMSO-d6): δ 8.45 (m, 1H), 7.55 (m, 1H), 7.42 (s, 1H), 7.31 (m, 2H), 7.05 (s, 1H), 6.93 (s, 1H), 3.95 (m, 4H), 3.86 (s, 2H), 3.83 (m, 4H), 2.84 (s, 3H), 2.42-2.63 (m, 8H), 1.08 (s, 6H)

후처리

  1. extractionThe aqueous layer was extracted with EtOAc
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by RP-HPLC

출처 및 근거

ORD 기록
ord-a48538c20e6c49e9a51d69667cf40a47
출처 데이터셋
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08394796B2

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