Pyridine → HCID 66611143, compound

HRID 1621866Notes

Reaction equation

HRID 1621866 reaction equation
[Cl-].O[NH3+].[CH3:4][O:5][C:6]1[CH:47]=[CH:46][C:9]([CH2:10][N:11]([CH2:37][C:38]2[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=2)[C:12]2[N:17]=[C:16]([CH3:18])[N:15]=[C:14]([C:19]3[C:20]([NH:27][C:28]4[CH:29]=[N:30][C:31]([O:35][CH3:36])=[C:32]([F:34])[CH:33]=4)=[N:21][CH:22]=[C:23]([CH:26]=3)[CH:24]=O)[N:13]=2)=[CH:8][CH:7]=1.[N:48]1C=CC=CC=1.C(OC(=O)C)(=O)C>CN(C=O)C.CO.O>[CH3:45][O:44][C:41]1[CH:40]=[CH:39][C:38]([CH2:37][N:11]([CH2:10][C:9]2[CH:8]=[CH:7][C:6]([O:5][CH3:4])=[CH:47][CH:46]=2)[C:12]2[N:17]=[C:16]([CH3:18])[N:15]=[C:14]([C:19]3[C:20]([NH:27][C:28]4[CH:29]=[N:30][C:31]([O:35][CH3:36])=[C:32]([F:34])[CH:33]=4)=[N:21][CH:22]=[C:23]([CH:26]=3)[C:24]#[N:48])[N:13]=2)=[CH:43][CH:42]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 21645Hydroxylamine HClHCID 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 66611143HCID 66611143, compoundYield 75.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A dark brown solution of hydroxyammonium chloride (0.700 g, 10.07 mmol), 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinaldehyde (Example 143, 2.00 g, 3.36 mmol) and pyridine (0.815 mL, 10.07 mmol) in 15 mL DMF was allowed to stir 2 h. The reaction was partitioned between water and EtOAc. The organic layer was washed with water 2 times, saturated aqueous NaCl once, and the organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give an orange solid, 2.0 g. This was treated with acetic anhydride (15.84 mL, 168 mmol), and the flask fitted with a water-cooled reflux condenser, and placed in an oil bath. The reaction was heated to reflux for 5 h, and then the reaction was cooled and stirred overnight. The slurry was treated with 80 mL MeOH, filtered and dried in vacuo to give 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinonitrile (1.50 g, 2.53 mmol, 75% yield) as a green-brown solid. m/z (ESI, +ve ion) 593 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 12.46 (s, 1H), 8.99 (d, J=2.3 Hz, 1H), 8.52 (d, J=2.3 Hz, 1H), 7.99 (d, J=2.3 Hz, 1H), 7.92 (dd, J=11.7, 2.2 Hz, 1H), 7.12-7.25 (m, 4H), 6.82-6.94 (m, 4H), 4.88 (s, 2H), 4.82 (s, 2H), 4.04 (s, 3H), 3.82 (s, 3H), 3.81 (s, 3H), 2.61 (s, 3H).

Workup

  1. customThe reaction was partitioned between water and EtOAc
  2. washThe organic layer was washed with water 2 times, saturated aqueous NaCl once
  3. dry with materialthe organics were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give an orange solid, 2.0 g
  7. temperaturecooled
  8. temperaturereflux condenser
  9. customplaced in an oil bath
  10. temperatureThe reaction was heated
  11. temperatureto reflux for 5 h
  12. temperaturethe reaction was cooled
  13. stirringstirred overnight
  14. filtrationfiltered
  15. customdried in vacuo

Sources & evidence

ORD record
ord-a26d108fa0b1456ab2c8127cdf1769db
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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