Trifluoroacetic acid → N5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)pyridine-2,5-diamine

HRID 1621692노트

반응식

HRID 1621692 반응식
[CH3:1][O:2][C:3]1[CH:58]=[CH:57][C:6]([CH2:7][N:8]([CH2:48][C:49]2[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][CH:50]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:33][C:34]4[CH:35]=[CH:36][C:37]([NH:40]C(=O)OC(C)(C)C)=[N:38][CH:39]=4)=[N:18][CH:19]=[C:20]([CH2:22][N:23]4[CH2:28][CH2:27][N:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:25][CH2:24]4)[CH:21]=3)[N:10]=2)=[CH:5][CH:4]=1.C(O)(C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:56][O:55][C:52]1[CH:51]=[CH:50][C:49]([CH2:48][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:58][CH:57]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:33][C:34]4[CH:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=4)=[N:18][CH:19]=[C:20]([CH2:22][N:23]4[CH2:24][CH2:25][N:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:27][CH2:28]4)[CH:21]=3)[N:10]=2)=[CH:54][CH:53]=1

참가 물질

5

반응물 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 66611381Tert-butyl 5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)pyridin-2-ylcarbamate

생성물 1

HCID 66611149N5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)pyridine-2,5-diamine수율 82.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

tert-Butyl 5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)pyridin-2-ylcarbamate (0.306 g, 0.377 mmol) was dissolved into DCM (5 mL total) in two 20 mL scintillation vials. TFA (2.5 mL total) was added and the solutions were stirred at rt for 3 h. The reaction mixtures were combined and poured into 20 mL of saturated aqueous sodium bicarbonate. The aqueous phase was extracted with 25% iPrOH in CHCl3+1% NH4OH (2×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (25 g, eluent: iPrOH (w/10% NH4OH) in CHCl3 0%-20%) to give N5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)pyridine-2,5-diamine (0.221 g, 82% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 11.44 (br. s., 1H); 8.69 (br. s., 1H); 8.15-8.21 (m, 1H); 8.12 (br. s., 1H); 7.69-7.79 (m, 1H); 7.21 (d, J=8.61 Hz, 4H); 6.85 (dd, J=15.75, 8.51 Hz, 4H); 6.49 (d, J=8.80 Hz, 1H); 4.83 (d, J=15.85 Hz, 4H); 4.27 (br. s., 2H); 3.75-3.85 (m, 6H); 3.48 (br. s., 2H); 3.18 (br. s., 4H); 2.68-2.76 (m, 3H); 2.49-2.61 (m, 7H). m/z (ESI, +ve ion) 711.0 (M+H)+.

후처리

  1. customThe reaction mixtures
  2. extractionThe aqueous phase was extracted with 25% iPrOH in CHCl3+1% NH4OH (2×20 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel chromatography (25 g, eluent: iPrOH (w/10% NH4OH) in CHCl3 0%-20%)

출처 및 근거

ORD 기록
ord-836b7695ba8e4f418e74d9a958597d13
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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