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Dimethylformamide → 4-(3-[4-{8-(6-Fluoro-pyridin-3-yl)-4-morpholin-4-yl-quinazolin-2-yl]-phenyl}-ureido)-N,N-dimethyl-benzamide

HRID 2092556
ノート
印刷プレビュー

反応式

HRID 2092556 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](=[C:5]([C:18]3[CH:19]=[N:20][C:21]([F:24])=[CH:22][CH:23]=3)[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:25][N:26]([CH3:54])[C:27](=[O:53])[C:28]1[CH:33]=[CH:32][C:31]([NH:34][C:35]([NH:37][C:38]2[CH:43]=[CH:42][C:41](B3OC(C)(C)C(C)(C)O3)=[CH:40][CH:39]=2)=[O:36])=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[F:24][C:21]1[N:20]=[CH:19][C:18]([C:5]2[CH:6]=[CH:7][CH:8]=[C:9]3[C:4]=2[N:3]=[C:2]([C:41]2[CH:40]=[CH:39][C:38]([NH:37][C:35](=[O:36])[NH:34][C:31]4[CH:30]=[CH:29][C:28]([C:27]([N:26]([CH3:54])[CH3:25])=[O:53])=[CH:33][CH:32]=4)=[CH:43][CH:42]=2)[N:11]=[C:10]3[N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:23][CH:22]=1
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

7

反応物 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 67517701N,N-Dimethyl-4-{3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-ureido}-benzamideHCID 866657672-Chloro-8-(6-fluoro-pyridin-3-yl)-4-morpholin-4-yl-quinazoline

生成物 1

HCID 573350294-(3-[4-{8-(6-Fluoro-pyridin-3-yl)-4-morpholin-4-yl-quinazolin-2-yl]-phenyl}-ureido)-N,N-dimethyl-benzamide
収率 7%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒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-8-(6-fluoro-pyridin-3-yl)-4-morpholin-4-yl-quinazoline (70 mg, 0.000203 mol), N,N-dimethyl-4-{3-{4-(4,4,5,5,-tetramethyl-[1,3,2] dioxaborolan-2-yl)-phenyl]-ureido]-benzamide (100 mg, 0.0002436 mol), cesium carbonate (133 mg, 0.000406 mol), DMF (3.5 mL) and water (0.9 mL) were added. The reaction mixture was degassed with nitrogen for 5-10 min. To the same reaction flask, Pd(PPh3)2Cl2 (7 mg, 0.0000101 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, 2% MeOH in chloroform) to yield the title compound as a light yellow solid [8 mg, 7%]. 1H NMR (400 MHz, DMSO-d6): δ 8.99 (s, 1H), 8.95 (s, 1H), 8.60 (s, 1H), 8.43 (m, 1H), 8.28 (d, J=8.8 Hz, 2H), 8.07 (d, J=8.4 Hz, 1H), 7.95 (d, J=7.2 Hz, 1H), 7.58 (m, 3H), 7.49 (m, 2H), 7.39 (m, 3H), 3.84 (s, 8H), 2.95 (s, 6H); LC-MS (ESI): Calculated mass: 591.2; Observed mass: 591.9 [M+H]+ (RT: 1.53 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-99edf89b5fe0496286d8a73e793ec989
出典データセット
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08440662B2

反応ノート

読み込み中…

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