Hydrochloric Acid → 4-(2-(6-Chloropyridin-3-ylamino)pyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1811837

反応式

HRID 1811837 の反応式
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH2:11][C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[N:16][CH:17]=1.F[C:20]1[C:25]([C:26]2[N:31]=[C:30]([CH3:32])[N:29]=[C:28]([N:33]([CH2:43][C:44]3[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][CH:45]=3)[CH2:34][C:35]3[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=3)[N:27]=2)=[CH:24][CH:23]=[CH:22][N:21]=1.Cl>C1COCC1.CCOC(C)=O.O>[Cl:18][C:15]1[N:16]=[CH:17][C:12]([NH:11][C:20]2[C:25]([C:26]3[N:31]=[C:30]([CH3:32])[N:29]=[C:28]([N:33]([CH2:34][C:35]4[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=4)[CH2:43][C:44]4[CH:45]=[CH:46][C:47]([O:50][CH3:51])=[CH:48][CH:49]=4)[N:27]=3)=[CH:24][CH:23]=[CH:22][N:21]=2)=[CH:13][CH:14]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 793055-Amino-2-chloropyridine2 回HCID 2733832Lithium Hexamethyldisilazide2 回HCID 595482404-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

生成物 1

HCID 595482274-(2-(6-Chloropyridin-3-ylamino)pyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine収率 70.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

1.0 M LHMDS in THF (600 μL, 0.600 mmol) was added to a solution of 5-amino-2-chloropyridine (49 mg, 0.381 mmol) and 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (80 mg, 0.180 mmol) in THF (4 mL) under nitrogen at rt. A dark orange mixture formed. After 1.5 h, the mixture was heated to about 50° C. After overnight, more 5-amino-2-chloropyridine (49 mg, 0.381 mmol) and LHMDS (600 μL, 0.600 mmol) were added. The reaction mixture was heated for another 2 h and cooled to rt. The mixture was neutralized with HCl (5 N, 0.3 mL) and diluted with EtOAc (10 mL) and water (10 mL). The aqueous layer was extracted with DCM twice and the combined organic was dried over Na2SO4 and concentrated. The residue was purified on silica (10-80% EtOAc in hexane) to give a yellow oil (70 mg). LCMS (ES, pos.): calcd for C30H28FN7O2: 553.2. found: 554.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 12.19 (s, 1H); 8.84 (dd, J=7.83, 1.76 Hz, 1H); 8.47 (d, J=2.74 Hz, 1H); 8.33 (dd, J=4.70, 1.76 Hz, 1H); 8.26 (dd, J=8.71, 2.84 Hz, 1H); 7.16-7.24 (m, 5H); 6.80-6.91 (m, 5H); 4.84 (s, 4H); 3.80 (d, J=5.87 Hz, 6H); 2.59 (s, 3H).

後処理

  1. customA dark orange mixture formed
  2. waitAfter overnight
  3. temperatureThe reaction mixture was heated for another 2 h
  4. temperaturecooled to rt
  5. extractionThe aqueous layer was extracted with DCM twice
  6. dry with materialthe combined organic was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified on silica (10-80% EtOAc in hexane)

出典と根拠

ORDレコード
ord-e940dddd4a3a4c0198962b735c1ef1b2
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

関連ノート

読み込み中…