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

HRID 712411
ノート
印刷プレビュー

反応式

HRID 712411 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:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:35][CH3:36])=[C:27]([O:30][CH2:31][CH2:32][CH2:33]Cl)[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:15]=[CH:16][C:17]=1[F:18])#[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:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:35][CH3:36])=[C:27]([O:30][CH2:31][CH2:32][CH2:33][N:8]4[CH2:7][CH:6]5[O:1][CH2:2][CH2:3][O:4][CH:5]5[CH2:9]4)[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:15]=[CH:16][C:17]=1[F:18])#[CH:11]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 82418726hexahydro-2H-[1,4]dioxino[2,3-c]pyrroleHCID 86729471N-(3-ethynyl-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine

生成物 1

HCID 86729472N-(3-ethynyl-4-fluorophenyl)-7-methoxy-6-(3-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl) propoxy)quinazolin-4-amine収率 44%

試薬・触媒・溶媒 2

HCID 67553
Tetrabutylammonium 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 (0.40 g, 3.01 mmol, 1.0 eq), N-(3-ethynyl-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine (0.87 g, 2.25 mmol, 0.75 eq), anhydrous K2CO3 (1.24 g, 9.0 mmol, 3.0 eq) and tetrabutylammonium iodide (55 mg, 0.15 mmol, 0.05 eq) in DMF (10 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 filtered. The filtrate was concentrated in vacuo and 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 (0.47 g, 44.00%), HPLC: 96.10%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 480.1 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.05 (2H, m), 2.68 (2H, m), 2.72 (2H, m), 2.95 (2H, dd, J=3.6, 10.0 Hz), 3.06 (1H, br s), 3.56 (2H, m), 3.76 (2H, m), 3.95 (3H, s), 4.08 (2H, m), 4.15 (2H, t, J=8.4 Hz), 7.20 (1H, t, J=8.8 Hz), 8.07-8.15 (2H, m), 8.43 (1H, s), 8.64 (1H, s) 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. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by a silica gel column chromatography (20:1 (v/v) CH2Cl2/CH3OH)
  10. customto give the crude product, which
  11. customwas recrystallized from CH2Cl2/PE

出典と根拠

ORDレコード
ord-139054bd68e64eba82ffc4f31a126fdc
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09181277B2

反応ノート

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