Toluene → 1-(4-(7-(5-Methylfuran-2-yl)-4-morpholino-quinazolin-2-yl)phenyl)-3-(4-(2-oxopyrrolidin-1-yl)phenyl)urea

HRID 517480

反応式

HRID 517480 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.[O:24]=[C:25]1[CH2:29][CH2:28][CH2:27][N:26]1[C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37]([NH:39][C:40]2[CH:45]=[CH:44][C:43](B3OC(C)(C)C(C)(C)O3)=[CH:42][CH:41]=2)=[O:38])=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1>O.CCO>[CH3:23][C:20]1[O:19][C:18]([C:6]2[CH:5]=[C:4]3[C:9]([C:10]([N:12]4[CH2:17][CH2:16][O:15][CH2:14][CH2:13]4)=[N:11][C:2]([C:43]4[CH:44]=[CH:45][C:40]([NH:39][C:37]([NH:36][C:33]5[CH:34]=[CH:35][C:30]([N:26]6[CH2:27][CH2:28][CH2:29][C:25]6=[O:24])=[CH:31][CH:32]=5)=[O:38])=[CH:41][CH:42]=4)=[N:3]3)=[CH:8][CH:7]=2)=[CH:22][CH:21]=1

参加物

7

反応物 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 675173641-(4-(2-Oxopyrrolidin-1-yl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ureaHCID 866657782-Chloro-7-(5-methyl-furan-2-yl)-4-morpholin-4-yl-quinazoline

生成物 1

HCID 675143031-(4-(7-(5-Methylfuran-2-yl)-4-morpholino-quinazolin-2-yl)phenyl)-3-(4-(2-oxopyrrolidin-1-yl)phenyl)urea収率 7%

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 (0.12 g, 0.00036 mol; prepared as described in Example 2; Scheme 6B), 1-(4-(2-oxopyrrolidin-1-yl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (0.184 g, 0.00043 mol; prepared according to the methods described in Scheme 9), cesium carbonate (0.296 g, 0.0009 mol), toluene (7 mL), EtOH (7 mL) and water (3 mL) were added. The reaction mixture was degassed with nitrogen for 5-10 min. To the same reaction flask, Pd (PPh3)2Cl2 (0.0128 g, 0.000018 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 95° C. for 3 h. The reaction mixture was cooled and diluted with chloroform. The organic layer was separated, washed with water, brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to afford the crude product. The crude product was purified by flash column chromatography using 230-400 silica gel, 2% MeOH in chloroform. The compound was further purified by prep TLC using 4% MeOH in chloroform to yield the title compound [0.015 g, 7%]. 1H NMR (300 MHz, DMSO-d6): δ 8.92 (s, 1H), 8.75 (s, 1H), 8.43 (d, J=7.2 Hz, 2H), 8.02 (d, J=8.1 Hz, 2H), 7.75 (d, J=8.4 Hz, 1H), 7.62 (t, J=8.7 Hz, 4H), 7.48 (d, J=9 Hz, 2H), 7.17 (d, J=3.3 Hz, 1H), 6.32 (d, J=2.4 Hz, 1H), 3.83 (m, 10H), 2.47 (d, J=8.4 Hz, 2H), 2.41 (s, 3H), 2.08 (m, 2H); LC-MS (ESI): Calculated mass: 588.2; Observed mass: 589.2 (RT: 0.13 min).

後処理

  1. customprepared
  2. additionwere added
  3. customThe reaction mixture was degassed with nitrogen for 5-10 min
  4. customagain degassed with nitrogen for 5-10 min
  5. temperatureThe reaction mixture was cooled
  6. additiondiluted with chloroform
  7. customThe organic layer was separated
  8. washwashed with water, brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe solvent was removed under reduced pressure
  11. customto afford the crude product
  12. customThe crude product was purified by flash column chromatography
  13. customThe compound was further purified by prep TLC

出典と根拠

ORDレコード
ord-a81d3bd6d8774afda17ae31ca0500efa
出典データセット
uspto-grants-2015_08
特許番号
US09115092B2

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