Sodium Cyanide → (5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)(4-hydroxypiperidin-1-YL)methanone

HRID 1812050Notes

Reaction equation

HRID 1812050 reaction equation
[CH3:1][O:2][C:3]1[CH:44]=[CH:43][C:6]([CH2:7][N:8]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=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:32][CH3:33])=[C:29]([F:31])[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+].[NH:48]1[CH2:53][CH2:52][CH:51]([OH:54])[CH2:50][CH2:49]1>C1COCC1.[O-2].[Mn+4].[O-2]>[CH3:42][O:41][C:38]1[CH:37]=[CH:36][C:35]([CH2:34][N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:44][CH:43]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:23]=[C:20]([C:21]([N:48]4[CH2:53][CH2:52][CH:51]([OH:54])[CH2:50][CH2:49]4)=[O:22])[CH:19]=[N:18][C:17]=3[NH:24][C:25]3[CH:26]=[N:27][C:28]([O:32][CH3:33])=[C:29]([F:31])[CH:30]=3)[N:10]=2)=[CH:40][CH:39]=1

Participants

6

Reactant 3

HCID 8929Sodium Cyanide2×HCID 79341Piperidin-4-olHCID 715003625-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinaldehyde

Product 1

HCID 66611784(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)(4-hydroxypiperidin-1-YL)methanone

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinaldehyde (0.054 g, 0.091 mmol) in THF (1.0 mL) at room temperature was treated with sodium cyanide (4.44 mg, 0.091 mmol) (Sigma-Aldrich), piperidin-4-ol (0.046 g, 0.453 mmol) (Aldrich) and manganese (IV) oxide (0.118 g, 1.360 mmol) (Sigma-Aldrich). The mixture was stirred at room temperature. After 1 h the reaction was incomplete, so a few granules of NaCN, and another 15 equiv. of manganese(IV) oxide (0.118 g, 1.360 mmol) were added. The mixture was stirred at room temperature for 18 h, then filtered through Celite® (diatomaceous earth). The organic layer was washed with water, then brine, dried over MgSO4, filtered and concentrated to give the title compound as a yellow film (85%). 1H NMR (400 MHz, d6-DMSO) δ 11.86 (s, 1H); 8.77 (d, J=2.3 Hz, 1H); 8.38 (d, J=2.3 Hz, 1H); 8.02-8.11 (m, 2H); 7.23-7.32 (m, 2H); 7.19 (m, J=8.6 Hz, 2H); 6.91 (m, 2H); 6.83 (d, J=8.8 Hz, 2H); 4.72-4.87 (m, 5H); 3.90-3.95 (m, 3H); 3.66-3.76 (m, 8H); 3.17-3.28 (m, 2H); 2.58 (s, 3H); 1.71 (br. s., 2H); 1.36 (br. s., 2H). m/z (ESI, +ve ion) 695.0 (M+H)+.

Workup

  1. stirringThe mixture was stirred at room temperature for 18 h
  2. filtrationfiltered through Celite® (diatomaceous earth)
  3. washThe organic layer was washed with water
  4. dry with materialbrine, dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-7499e957dc0f46a895531778d65f14e3
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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