Toluene → N,N-Dimethyl-4-(3-{4-[7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazolin-2-yl]-phenyl}-ureido)-benzamide

HRID 2092539

反応式

HRID 2092539 の反応式
Cl[C:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([C:18]3[O:19][C:20]([CH3:23])=[CH:21][CH:22]=3)=[CH:7][CH:8]=2)[N:3]=1.[CH3:24][N:25]([CH3:53])[C:26](=[O:52])[C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH:36][C:37]2[CH:42]=[CH:41][C:40](B3OC(C)(C)C(C)(C)O3)=[CH:39][CH:38]=2)=[O:35])=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O.CCO>[CH3:24][N:25]([CH3:53])[C:26](=[O:52])[C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH:36][C:37]2[CH:38]=[CH:39][C:40]([C:2]3[N:11]=[C:10]([N:12]4[CH2:17][CH2:16][O:15][CH2:14][CH2:13]4)[C:9]4[C:4](=[CH:5][C:6]([C:18]5[O:19][C:20]([CH3:23])=[CH:21][CH:22]=5)=[CH:7][CH:8]=4)[N:3]=3)=[CH:41][CH:42]=2)=[O:35])=[CH:29][CH:28]=1

参加物

7

反応物 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 67517701N,N-Dimethyl-4-{3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-ureido}-benzamideHCID 866657782-Chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazoline

生成物 1

HCID 57334873N,N-Dimethyl-4-(3-{4-[7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazolin-2-yl]-phenyl}-ureido)-benzamide収率 31.3%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
95 °C

実験手順

To a 50 mL round bottom flask, 2-chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazoline (1.4 g, 0.0036 mol), N,N-dimethyl-4-{3-{4-(4,4,5,5,-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ureido}-benzamide (2.25 g, 0.0055 mol), sodium carbonate (0.775 g, 0.0073 mol), toluene (12 mL), EtOH (12 mL) and water (12 mL) were added. The reaction mixture was degassed with nitrogen for 5-10 min. To the same reaction flask, Pd (PPh3)2Cl2 (128 mg, 0.000023 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 95° C. for 2 h. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was removed under reduced pressure to afford the crude product. The crude product was purified using column chromatography (60-120 silica gel, 0-4% MeOH in chloroform) followed by preparative HPLC (0.1% TFA in water and ACN) to yield the title compound [0.65 g, 27%]. 1H NMR (400 MHz, DMSO-d6): δ 9.49 (brs, 1H), 9.27 (brs, 1H), 8.30 (d, J=8.8 Hz, 2H), 8.11 (t, J=9.2 Hz, 2H), 7.85 (d, J=8.8 Hz, 1H), 7.72 (d, J=8.8 Hz, 2H), 7.52 (d, J=8.8, 2H), 7.37 (d, J=8.4 Hz, 2H), 7.22 (d, J=3.2 Hz, 1H), 6.37 (s, 1H), 4.22 (brs, 4H), 3.83 (brs, 4H), 2.95 (s, 6H), 2.40 (s, 3H); LC-MS (ESI): Calculated mass: 576.2; Observed mass: 576.7 [M+H]+ (RT: 0.64 min).

後処理

  1. customThe reaction mixture was degassed with nitrogen for 5-10 min
  2. customagain degassed with nitrogen for 5-10 min
  3. temperatureThe reaction mixture was cooled
  4. additiondiluted with ethyl acetate
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customto afford the crude product
  9. customThe crude product was purified

出典と根拠

ORDレコード
ord-3543311e9ae6456d87d34f50825c2b31
出典データセット
uspto-grants-2013_05
特許番号
US08440662B2

関連ノート

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