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 1812229노트

반응식

HRID 1812229 반응식
[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]

참가 물질

4

반응물 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, 화합물

생성물 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-amine수율 73.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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, 2.2 Hz, 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).

후처리

  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

출처 및 근거

ORD 기록
ord-8e33e2852d624eaf8e12e5192b2cde1f
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362241B2

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