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Sodium triacetoxyborohydride → N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-6-(5-((4-((dimethylphosphinoyl)-methyl)piperazin-1-yl)methyl)furan-2-yl)quinazolin-4-amine

HRID 877100
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HRID 877100 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][CH:34]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([C:24]4[O:28][C:27]([CH:29]=O)=[CH:26][CH:25]=4)[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[CH:9][C:8]=1[Cl:31].[CH3:35][P:36]([CH2:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)([CH3:38])=[O:37].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][CH:34]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([C:24]4[O:28][C:27]([CH2:29][N:43]5[CH2:42][CH2:41][N:40]([CH2:39][P:36]([CH3:38])([CH3:35])=[O:37])[CH2:45][CH2:44]5)=[CH:26][CH:25]=4)[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[CH:9][C:8]=1[Cl:31]
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참가 물질

6

반응물 3

HCID 5049666Sodium triacetoxyborohydrideHCID 11181296(5-(4-(4-((3-Fluorobenzyl)oxy)-3-chloroanilino)-6-quinazolinyl)-2-furancarboxaldehydeHCID 203769071-[(Dimethylphosphoryl)methyl]piperazine

생성물 1

HCID 49856052N-(4-(3-fluorobenzyloxy)-3-chlorophenyl)-6-(5-((4-((dimethylphosphinoyl)-methyl)piperazin-1-yl)methyl)furan-2-yl)quinazolin-4-amine

시약·촉매·용매 2

HCID 176
Acetic Acid
촉매
HCID 6344Dichloromethane용매

실험 절차

5-(4-(4-(3-fluorobenzyloxy)-3-chlorophenylamino)quinazolin-6-yl)furan-2-carbaldehyde and 1-((dimethylphosphinoyl)methyl)piperazine were suspended in dichloromethane (20 mL). Sequentially, acetic acid (3 drops) and sodium triacetoxyborohydride (2 equiv.) were added at room temperature. The mixture was stirred at room temperature until the starting material disappeared. The reaction was quenched with 2N NaOH aqueous solution and extracted with dichloromethane. The combined organic layer and extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography, eluting with 20% methanol in dichloromethane to give the desired product as yellow crystalline solid. LCMS ESI(+) m/z: 635 (M+1). 1H NMR (300 MHz, CD3OD) δ 8.59 (s, 1H), 8.44 (s, 1H), 8.11 (m, 1H), 7.89 (m, 1H), 7.72 (m, 1H), 7.57 (m, 1H), 7.38 (m, 1H), 7.26 (m, 2H), 7.08 (m, 2H), 6.90 (d, 1H), 6.46 (d, 1H), 5.17 (s, 2H), 3.66 (s, 2H), 2.80 (m, 2H), 2.68 (m, 8H), 1.57 (d, 6H).

후처리

  1. customThe reaction was quenched with 2N NaOH aqueous solution
  2. extractionextracted with dichloromethane
  3. dry with materialThe combined organic layer and extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography
  7. washeluting with 20% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-eb6c0e9860404e2588045bccff14b069
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08987284B2

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