Morpholine → 2-(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-morpholinopropanenitrile

HRID 1812228ノート

反応式

HRID 1812228 の反応式
[CH3:1][O:2][C:3]1[CH:45]=[CH:44][C:6]([CH2:7][N:8]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([C:32](=O)[CH3:33])[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=3)[N:10]=2)=[CH:5][CH:4]=1.[NH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.[C:52]([Al](CC)CC)#[N:53].C([O-])(O)=O.[Na+]>C(Cl)Cl.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C.CCOC(C)=O>[CH3:43][O:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:45][CH:44]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([C:32]([N:46]4[CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)([CH3:33])[C:52]#[N:53])[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=3)[N:10]=2)=[CH:37][CH:38]=1

参加物

8

反応物 4

HCID 8083MorpholineHCID 516892Sodium Bicarbonate2 回HCID 16683962(cyano-C)diethylaluminiumHCID 666002411-(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)ethanone

生成物 1

HCID 666114652-(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-morpholinopropanenitrile収率 100%

試薬・触媒・溶媒 3

HCID 178460666HCID 178460666、化合物触媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

A solution of 1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (Example 271, 0.564 g, 0.925 mmol) and morpholine (0.201 mL, 2.313 mmol) in DCM (4.5 mL) was treated with tetraisopropoxytitanium (0.678 mL, 2.313 mmol). The reaction was sealed and stirred rapidly overnight. Cyanodiethylaluminum (1.0 M in toluene; 2.313 mL, 2.313 mmol) was added and the reaction was resealed and stirred overnight. EtOAc was added followed by sat'd NaHCO3 (cautiously). An exotherm and effervescence was observed, so the reaction was poured onto ice and treated with EtOAc and sat'd aq. NaHCO3. The aqueous layer was extracted with EtOAc (2×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to give 2-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-morpholinopropanenitrile (0.650 g, 0.921 mmol, 100% yield) as a yellow solid. m/z (ESI, +ve ion) 706 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.99 (br. s., 1H); 9.00 (d, J=2.5 Hz, 1H); 8.50 (d, J=2.5 Hz, 1H); 8.03 (dd, J=12.1, 2.2 Hz, 1H); 7.97 (d, J=2.2 Hz, 1H); 7.17-7.26 (m, 4H); 6.82-6.93 (m, 4H); 4.73-5.01 (m, 4H); 4.03 (s, 3H); 3.82 (s, 3H); 3.79 (s, 3H); 3.61-3.71 (m, 4H); 2.64-2.76 (m, 2H); 2.60 (s, 3H); 2.44-2.54 (m, 2H); 1.75 (s, 3H).

後処理

  1. customThe reaction was sealed
  2. stirringstirred overnight
  3. additionwas poured onto ice
  4. extractionThe aqueous layer was extracted with EtOAc (2×)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-1810390a03d644619bd0c154c58d66f7
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

反応ノート

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