N,N-Diethylaniline → N-{4-[(2-amino-6-methyl-4-pyrimidinyl)amino]phenyl}-5-nitro-2-pyridinecarboxamide

HRID 547566Notes

Reaction equation

HRID 547566 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]([OH:12])=O)=[N:8][CH:9]=1)([O-:3])=[O:2].Cl.[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]2[CH:27]=[C:26]([CH3:28])[N:25]=[C:24]([NH2:29])[N:23]=2)=[CH:17][CH:16]=1.C(N(CC)C1C=CC=CC=1)C>O=P(Cl)(Cl)Cl>[NH2:29][C:24]1[N:23]=[C:22]([NH:21][C:18]2[CH:19]=[CH:20][C:15]([NH:14][C:10]([C:7]3[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=3)=[O:12])=[CH:16][CH:17]=2)[CH:27]=[C:26]([CH3:28])[N:25]=1

Participants

5

Reactant 3

HCID 7061N,N-DiethylanilineHCID 5204885-Nitropicolinic acidHCID 86621654HCID 86621654, compound

Product 1

HCID 59458006N-{4-[(2-amino-6-methyl-4-pyrimidinyl)amino]phenyl}-5-nitro-2-pyridinecarboxamideYield 33.9%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
20 °C

Procedure

5-Nitropyridine-2-carboxylic acid 18 (1.06 g, 6.31 mmol) was refluxed in POCl3 (10 mL) for 1 h. (clear solution obtained), cooled to 20° C. and excess POCl3 was removed under vacuum. The resulting residue was dissolved in 1,4-dioxane ((20 mL) and added slowly to a suspension of 17 (1.44 g, 5.72 mmol) and N,N-diethylaniline (2.0 mL, 12.62 mmol) in 1,4-dioane (20 mL). The reaction mixture was stirred at 20° C. for 3 days. The resulting white precipitate was filtered and washed with more 1,4-dioxane. The solid was stirred in aqueous NH3 (20 mL) and the resulting red precipitate was filtered, washed with water and recrystallized from MeOH to give 20 (708 mg, 31%); mp (MeOH)>290° C.; 1H NMR ([(CD3)2SO] δ 10.74 (1 H, NH), 9.43 (dd, J=2.6, 0.5 Hz, 1 H, H-6), 8.96 (s, 1 H, NH), 8.81 (dd, J=8.6, 2.6 Hz, 1 H, H-4), 8.38 (dd, J=8.6, 0.6 Hz, 1 H, H-3), 7.81 (d, J=9.0 Hz, 2 H, H-2′ H-6′), 7.70 (d, J=9.1 Hz, 2 H, H-3′,5′), 6.09 (s, 2 H, NH2), 5.87 (s, 1 H, H-5″), 2.09 (s, 3 H, CH3); HRMS (FAB+) calc. for C17H16N7O3 (M+1) m/z 366.1315, found 366.1314; Anal. calc. for C17H15N7O3.0.25 MeOH: C, 55.5; H, 4.4: N, 26.3; found, C, 55.7; H, 4.5; N, 26.2%.

Workup

  1. custom(clear solution obtained)
  2. customexcess POCl3 was removed under vacuum
  3. dissolutionThe resulting residue was dissolved in 1,4-dioxane ((20 mL)
  4. filtrationThe resulting white precipitate was filtered
  5. washwashed with more 1,4-dioxane
  6. stirringThe solid was stirred in aqueous NH3 (20 mL)
  7. filtrationthe resulting red precipitate was filtered
  8. washwashed with water
  9. customrecrystallized from MeOH

Sources & evidence

ORD record
ord-899f08e1f69b44bb8644d0a667c4b7b6
Source dataset
uspto-grants-2011_05
Patent number
US07939546B2

Reaction notes

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