Potassium Carbonate → N-(3-ethynylphenyl)-7-methoxy-6-(3-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl) propoxy)quinazolin-4-amine

HRID 712407ノート

反応式

HRID 712407 の反応式
[O:1]1[CH:6]2[CH2:7][NH:8][CH2:9][CH:5]2[O:4][CH2:3][CH2:2]1.[C:10]([C:12]1[CH:13]=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:34][CH3:35])=[C:26]([O:29][CH2:30][CH2:31][CH2:32]Cl)[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1)#[CH:11].C([O-])([O-])=O.[K+].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[C:10]([C:12]1[CH:13]=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:34][CH3:35])=[C:26]([O:29][CH2:30][CH2:31][CH2:32][N:8]4[CH2:7][CH:6]5[O:1][CH2:2][CH2:3][O:4][CH:5]5[CH2:9]4)[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1)#[CH:11]

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 82418726hexahydro-2H-[1,4]dioxino[2,3-c]pyrroleHCID 867294706-(3-chloropropoxy)-N-(3-ethynylphenyl)-7-methoxyquinazolin-4-amine

生成物 1

HCID 71573027N-(3-ethynylphenyl)-7-methoxy-6-(3-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl) propoxy)quinazolin-4-amine収率 50%

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

A mixture of hexahydro-2H-[1,4]dioxino[2,3-c]pyrrole (0.31 g, 2.40 mmol, 1.20 eq), N-(3-ethynylphenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine (0.74 g, 2.00 mmol, 1.00 eq), anhydrous K2CO3 (1.00 g, 7.20 mmol, 3.60 eq) and tetrabutylammonium iodide (37 mg, 0.10 mmol, 0.05 eq) in DMF (8 mL) was heated at 70° C. for 11 h. The reaction mixture was cooled to room temperature and quenched with water (10 mL). The resulted mixture was diluted with EtOAc (20 mL) and the organic phase was separated from the mixture. The water phase was extracted with EtOAc (20 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (20:1 (v/v) CH2Cl2/CH3OH) to give the crude product, which was recrystallized from CH2Cl2/PE to afford the title compound as a pale yellow solid (0.46 g, 50.00%), HPLC: 96.10%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 461.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.98 (3H, s), 2.09 (2H, m), 2.73 (2H, m), 2.78 (2H, m), 2.97 (2H, dd, J=4.4, 10.4 Hz), 3.09 (1H, s), 3.55 (2H, m), 3.79 (2H, m), 3.99 (3H, s), 4.11 (2H, m), 4.22 (2H, t, J=6.8 Hz), 7.24 (2H, m), 7.25-7.28 (1H, m), 7.35 (1H, t, J=8.0 Hz), 7.67 (1H, br s), 7.80 (1H, m), 786 (1H, m) ppm.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with water (10 mL)
  3. additionThe resulted mixture was diluted with EtOAc (20 mL)
  4. customthe organic phase was separated from the mixture
  5. extractionThe water phase was extracted with EtOAc (20 mL×3)
  6. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (20:1 (v/v) CH2Cl2/CH3OH)
  9. customto give the crude product, which
  10. customwas recrystallized from CH2Cl2/PE

出典と根拠

ORDレコード
ord-e8717d0494f94908b0cf40aaa33b6144
出典データセット
uspto-grants-2015_11
特許番号
US09181277B2

反応ノート

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