Diethyl Ether → Methyl 5-azido-2,6-bis(4-methoxyphenyl)pyrimidine-4-carboxylate

HRID 2410735Notes

Reaction equation

HRID 2410735 reaction equation
[NH2:1][C:2]1[C:3]([C:24]([O:26][CH3:27])=[O:25])=[N:4][C:5]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1.N([O-])=O.[Na+].[N-:32]=[N+:33]=[N-].[Na+].C(OCC)C>FC(F)(F)C(O)=O>[N:1]([C:2]1[C:3]([C:24]([O:26][CH3:27])=[O:25])=[N:4][C:5]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=[N:6][C:7]=1[C:8]1[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=1)=[N+:32]=[N-:33]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 23668193Sodium NitriteHCID 66604984Methyl 5-amino-2,6-bis(4-methoxyphenyl)pyrimidine-4-carboxylate

Product 1

HCID 86663016Methyl 5-azido-2,6-bis(4-methoxyphenyl)pyrimidine-4-carboxylateYield 82.8%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Methyl 5-amino-2,6-bis(4-methoxyphenyl)pyrimidine-4-carboxylate (393 mg, 1.08 mmol) was dissolved in trifluoroacetic acid (5 mL) and the yellow solution was cooled in an ice bath. Solid sodium nitrite (148 mg, 2.15 mmol) was added with stirring to give a dark red mixture. After 10 minutes, solid sodium azide (699 mg, 10.8 mmol) was added followed by diethyl ether (5 mL). After and additional 20 minutes the reaction was partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution) to neutralize the acid. The organic phase was separated, washed with brine, dried with sodium sulfate, and the solvent removed to leave methyl 5-azido-2,6-bis(4-methoxyphenyl)pyrimidine-4-carboxylate (350 mg) as a solid. 1H NMR (CDCl3) δ ppm 8.42 (2H, d, J=9.16 Hz), 8.02 (2H, d, J=9.16 Hz), 7.03 (2H, d, J=8.85 Hz), 6.96 (2H, d, J=9.16 Hz), 4.07 (3H, s), 3.88 (3H, s), 3.85 (3H, s).

Workup

  1. temperaturethe yellow solution was cooled in an ice bath
  2. customto give a dark red mixture
  3. customAfter and additional 20 minutes the reaction was partitioned between EtOAc and sufficient saturated aqueous NaHCO3 solution (gas evolution)
  4. customThe organic phase was separated
  5. washwashed with brine
  6. dry with materialdried with sodium sulfate
  7. customthe solvent removed

Sources & evidence

ORD record
ord-299c61fcd44943c380ada9bed311c9e5
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…