Sodium Cyanide → (5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-(methylsulfonyl)piperazin-1-yl)methanone

HRID 1812231Notes

Reaction equation

HRID 1812231 reaction equation
[CH3:1][O:2][C:3]1[CH:43]=[CH:42][C:6]([CH2:7][N:8]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[C:17]([NH:24][C:25]4[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=4)=[N:18][CH:19]=[C:20]([CH:23]=3)[CH:21]=[O:22])[N:10]=2)=[CH:5][CH:4]=1.[C-]#N.[Na+].[CH3:47][S:48]([N:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1)(=[O:50])=[O:49]>C1COCC1.[O-2].[Mn+4].[O-2]>[CH3:41][O:40][C:37]1[CH:36]=[CH:35][C:34]([CH2:33][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:43][CH:42]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:23]=[C:20]([C:21]([N:54]4[CH2:55][CH2:56][N:51]([S:48]([CH3:47])(=[O:50])=[O:49])[CH2:52][CH2:53]4)=[O:22])[CH:19]=[N:18][C:17]=3[NH:24][C:25]3[CH:26]=[N:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[N:10]=2)=[CH:39][CH:38]=1

Participants

6

Reactant 3

HCID 8929Sodium CyanideHCID 7091611-(Methylsulfonyl)piperazineHCID 601552675-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde

Product 1

HCID 66611409(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-(methylsulfonyl)piperazin-1-yl)methanoneYield 27.5%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)nicotinaldehyde (Example 144, 1.00 g, 1.731 mmol), activated manganese (IV) oxide (<5 micron; 4.52 g, 51.9 mmol), sodium cyanide (0.053 mL, 1.731 mmol) and 1-(methylsulfonyl)piperazine (0.711 g, 4.33 mmol) in THF (15 mL) was stirred rapidly under nitrogen for 72 h. The reaction was filtered through Celite® (diatomaceous earth) rinsing with 10% MeOH/DCM followed by EtOAc. The filtrate was concentrated and adsorbed onto 5 g silica gel and passed through an 80 g column using 20-100% EtOAc/hexanes to give (5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)(4-(methylsulfonyl)piperazin-1-yl)methanone (0.352 g, 0.476 mmol, 27.5% yield) as a yellow foam. m/z (ESI, +ve ion) 740 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 12.02 (s, 1H); 8.91 (d, J=2.3 Hz, 1H); 8.42 (d, J=2.5 Hz, 1H); 8.29 (d, J=2.5 Hz, 1H); 7.90 (dd, J=8.8, 2.7 Hz, 1H); 7.11-7.24 (m, 4H); 6.80-6.94 (m, 4H); 6.75 (d, J=9.0 Hz, 1H); 4.85 (s, 2H); 4.82 (s, 2H); 3.95 (s, 3H); 3.82 (s, 3H); 3.80 (s, 3H); 3.71-3.78 (m, 4H); 3.17-3.25 (m, 4H); 2.70 (s, 3H); 2.60 (s, 3H).

Workup

  1. filtrationThe reaction was filtered through Celite® (diatomaceous earth)
  2. washrinsing with 10% MeOH/DCM
  3. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-15778777c6ce43d6902a8192808882bb
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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