Nitrogen → 5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde

HRID 1621570ノート

反応式

HRID 1621570 の反応式
O1CC[O:3][CH:2]1[C:6]1[CH:7]=[C:8]([C:13]2[N:18]=[C:17]([CH3:19])[N:16]=[C:15]([N:20]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[N:14]=2)[C:9](F)=[N:10][CH:11]=1.N#N.[CH3:41][O:42][C:43]1[N:48]=[CH:47][C:46]([NH2:49])=[CH:45][CH:44]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1C=CC=CC=1.C1COCC1.C(Cl)Cl>[CH3:29][O:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][N:20]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[C:15]2[N:16]=[C:17]([CH3:19])[N:18]=[C:13]([C:8]3[C:9]([NH:49][C:46]4[CH:47]=[N:48][C:43]([O:42][CH3:41])=[CH:44][CH:45]=4)=[N:10][CH:11]=[C:6]([CH:7]=3)[CH:2]=[O:3])[N:14]=2)=[CH:27][CH:26]=1

参加物

8

反応物 4

HCID 947NitrogenHCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 601549954-(5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

生成物 1

HCID 601552675-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde収率 61%

試薬・触媒・溶媒 3

HCID 241Benzene溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A stock solution of 4-(5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 143, Step 1) (5.85 g, 11.30 mmol) in benzene (50 mL) contained in a 250 mL round-bottomed flask with stir bar was frozen and lyophilized overnight (pale yellow solid obtained). The flask was opened to N2 and THF (50 mL) was added followed by 6-methoxypyridin-3-amine (1.332 mL, 12.43 mmol). The solution was cooled in an ice bath and LiHMDS (44 mL of a 1.0 M solution in THF, 44 mmol) was added. The mixture was stirred for 40 min and then quenched with water (3 mL) and concentrated to dryness. The residue was taken up in a mixture of DCM and 2N aqueous HCl and stirred for 30 min. The product was extracted into DCM from 2N HCl, washed with saturated aqueous NaHCO3, dried (MgSO4) and concentrated to give a brown solid. This was dissolved in DCM and purified by flash chrormatography (30% EtOAc, 10% DCM, 60% hexane) to give 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde (3.98 g, 6.89 mmol, 61.0% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.09 (s, 1H); 9.90 (s, 1H); 9.14 (d, J=2.35 Hz, 1H); 8.77 (d, J=2.35 Hz, 1H); 8.31 (d, J=2.74 Hz, 1H); 7.87 (dd, J=8.80, 2.74 Hz, 1H); 7.28 (d, J=8.61 Hz, 2H); 7.21 (d, J=8.80 Hz, 2H); 6.87-6.94 (m, 2H); 6.78-6.87 (m, 3H); 4.83 (d, J=7.24 Hz, 4H); 3.85 (s, 3H); 3.74 (s, 3H); 3.69 (s, 3H); 2.58 (s, 3H). m/z (ESI, +ve ion) 578 (M+H)+.

後処理

  1. temperaturewas frozen
  2. custom(pale yellow solid obtained)
  3. additionwas added
  4. temperatureThe solution was cooled in an ice bath
  5. stirringThe mixture was stirred for 40 min
  6. customquenched with water (3 mL)
  7. concentrationconcentrated to dryness
  8. additionThe residue was taken up in a mixture of DCM and 2N aqueous HCl
  9. stirringstirred for 30 min
  10. extractionThe product was extracted into DCM from 2N HCl
  11. washwashed with saturated aqueous NaHCO3
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. customto give a brown solid
  15. custompurified by flash chrormatography (30% EtOAc, 10% DCM, 60% hexane)

出典と根拠

ORDレコード
ord-efb3ce057f07415cb623575e601164f2
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

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