Acetic Acid → HCID 66612194, compound

HRID 1812270Notes

Reaction equation

HRID 1812270 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.CO.[C:47](O)(=[O:49])C.[C-]#N.[Na+]>C1COCC1.[O-2].[O-2].[Mn+4]>[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[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)[C:21]([O:49][CH3:47])=[O:22])[N:10]=2)=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 8929Sodium CyanideHCID 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 66612194HCID 66612194, compoundYield 50.9%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalyst2×HCID 8028TetrahydrofuranSolvent

Procedure

A slurry of 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinaldehyde (Example 143, 0.200 g, 0.336 mmol), manganese dioxide (0.584 g, 6.72 mmol), methanol (0.068 mL, 1.679 mmol), acetic acid (0.029 mL, 0.504 mmol), and sodium cyanide (0.082 g, 1.679 mmol) in 4 mL THF was stirred rapidly overnight. Manganese dioxide (0.584 g, 6.72 mmol) was added, the reaction was sealed, and stirred rapidly for 3 days. The reaction was filtered through Celite® (diatomaceous earth), rinsing with 10% MeOH/DCM. The residue was adsorbed onto 2 g silica gel, dried, and purified by silica gel chromatography (40 g column) using 0-100% EtOAc/hexane. The product-containing fractions were concentrated to afford methyl 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinate (0.107 g, 0.171 mmol, 50.9% yield) as a orange solid. m/z (ESI, +ve ion) 626 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 12.33 (br. s., 1H), 9.41 (d, J=2.3 Hz, 1H), 8.92 (d, J=2.3 Hz, 1H), 7.98 (d, J=2.3 Hz, 1H,) 7.90-7.97 (m, 1H), 7.16-7.25 (m, 4H), 6.82-6.92 (m, 4H), 4.90 (s, 2H), 4.84 (s, 2H,) 4.04 (s, 3H), 3.92 (s, 3H), 3.82 (s, 3H), 3.79 (s, 3H), 2.61 (s, 3H).

Workup

  1. customthe reaction was sealed
  2. filtrationThe reaction was filtered through Celite® (diatomaceous earth)
  3. washrinsing with 10% MeOH/DCM
  4. customdried
  5. custompurified by silica gel chromatography (40 g column)
  6. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-cb8285f34d924abfa3e9287f93e87679
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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