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 → 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621821ノート

反応式

HRID 1621821 の反応式
[CH3:1][O:2][C:3]1[CH:52]=[CH:51][C:6]([CH2:7][N:8]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[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:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)([CH3:35])[C:33]#N)[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.C[Mg]Br>C1COCC1>[F:29][C:27]1[CH:28]=[C:23]([NH:22][C:21]2[C:16]([C:11]3[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([N:8]([CH2:7][C:6]4[CH:51]=[CH:52][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH2:42][C:43]4[CH:44]=[CH:45][C:46]([O:49][CH3:50])=[CH:47][CH:48]=4)[N:10]=3)=[CH:17][C:18]([C:32]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)([CH3:33])[CH3:35])=[CH:19][N:20]=2)[CH:24]=[N:25][C:26]=1[O:30][CH3:31]

参加物

4

反応物 2

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-morpholinopropanenitrileHCID 178418573HCID 178418573、化合物

生成物 1

HCID 666111624-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine収率 73.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of 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 (0.500 g, 0.708 mmol) in THF (2 mL) at 0° C. was treated with methylmagnesium bromide (3.0 M in diethyl ether; 1.181 mL, 3.54 mmol). The cooling bath was removed after 10 min, and the reaction was allowed to warm to ambient temperature. After 2 h total, the reaction was cooled to 0° C. and quenched with EtOAc (1 mL) followed by ice and sat'd aq. NH4Cl. The reaction was partitioned between satd NH4Cl and DCM. The aqueous layer was extracted with DCM (3×) and the combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography using 10-80% EtOAc/hexane. The product-containing fractions were concentrated to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-morpholinopropan-2-yl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.363 g, 0.522 mmol, 73.7% yield) as a yellow solid. m/z (ESI, +ve ion) 695 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.86 (s, 1H); 8.96 (d, J=2.5 Hz, 1H); 8.47 (d, J=2.5 Hz, 1H); 8.13 (dd, J=12.5, 2.2Hz, 1H); 7.91-8.01 (m, 1H); 7.17-7.26 (m, 4H); 6.75-6.96 (m, 4H); 4.89 (s, 2H); 4.84 (s, 2H); 4.02 (s, 3H); 3.82 (s, 3H); 3.79 (s, 3H); 3.55-3.65 (m, 4H); 2.59 (s, 3H); 2.42-2.51 (m, 4H); 1.35 (s, 6H).

後処理

  1. customThe cooling bath was removed after 10 min
  2. temperaturethe reaction was cooled to 0° C.
  3. customquenched with EtOAc (1 mL)
  4. customThe reaction was partitioned between satd NH4Cl and DCM
  5. extractionThe aqueous layer was extracted with DCM (3×)
  6. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. additionThe material was treated with DCM
  10. custompurified by silica gel chromatography
  11. concentrationThe product-containing fractions were concentrated

出典と根拠

ORDレコード
ord-1d67853908f24ba38e593fc4a9f400bf
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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