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 1621692Notes

Reaction equation

HRID 1621692 reaction equation
[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

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 66611381HCID 66611381, compound

Product 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-diamineYield 82.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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)+.

Workup

  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%)

Sources & evidence

ORD record
ord-836b7695ba8e4f418e74d9a958597d13
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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