Acetic Anhydride → HCID 45485483, compound

HRID 1360367Notes

Reaction equation

HRID 1360367 reaction equation
[OH:1][CH2:2][N:3]([CH3:24])[N:4]=[N:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][N:10]=[C:9]2[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=1.[C:25](OC(=O)C)(=[O:27])[CH3:26]>N1C=CC=CC=1>[C:25]([O:1][CH2:2][N:3]([CH3:24])[N:4]=[N:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][N:10]=[C:9]2[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=1)(=[O:27])[CH3:26]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 58584320HCID 58584320, compound

Product 1

HCID 45485483HCID 45485483, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 4-(3′-chlorophenyl-amino)-6-aminoquinazoline (100 mg, 0.318 mmol) in acetonitrile (20 mL) kept at 0° C. in an ice bath, nitrosonium tetrafluoroborate (74.3 mg, 0.637 mmol) was added dropwise. The solution was stirred for 20 min and 0.9 mL of a mixture of methylamine 40% (0.075 mL, 0.954 mmol), formaldehyde 37% (0.75 mL, 9.54 mmol), and concentrated HCl (0.1 mL) was added all at once. The diazonium solution was subsequently alkalinized with potassium carbonate (400 mg, 2.86 mmol) and the precipitate was filtered to give a white solid contaminated with excess potassium carbonate. The precipitate was therefore re-suspended in THF and the resulting solution filtered. The organic solvent was further evaporated to give 6-(3-hydroxymethyl-3-methyl-triazenyl)-4-(3′-chlorophenyl-amino)quinazoline as a pure brown solid (90 mg, 73%). 6-(3-Hydroxymethyl-3-methyl-triazenyl)-4-(3′-chlorophenyl-amino)quinazoline (100 mg, 0.258 mmol) was dissolved in pyridine (2 mL) after which acetic anhydride (0.055 mL, 0.516 mmol) was slowly added. The solution was further kept on ice for 1.5 h and the pyridine evaporated as an azeotrope with toluene to give 6-(3-Acetoxymethyl-3-methyl-triazenyl)-4-(3′-chlorophenyl-amino)quinazoline as a pure brown residue (105 mg, 95%). 6-(3-Acetoxymethyl-3-methyl-triazenyl)-4-(3′-chlorophenyl-amino)quinazoline (100 mg, 0.260 mmol) was dissolved in anhydrous methanol (2.5 mL) and stirred at room temperature for 24 h. The methanol was then evaporated to provide the title compound 6-(3-methoxymethyl-3-methyl-triazenyl)-4-(3′-chlorophenyl-amino)quinazoline) as a pure brown residue (91 mg, 98%): EI m/z 357.0 (MH+), 253.2 (M-3-methoxymethyl-3-methyl-triazene); 1H NMR (400 MHz, DMSO-d6) d 9.94 (s, 1H, NH), 8.60 (s, 1H), 8.54 (s, 1H), 8.14 (s, 1H), 8.01 (d, 1H, J=9.2 Hz), 7.88 (d, 1H, J=6.8 Hz), 7.79 (d, 1H, J=9.2 Hz), 7.39 (t, 1H, J=6.6 Hz), 7.14 (d, 1H, J=9.2 Hz), 5.17 (s, 2H, CH2), 3.25 (s, 3H, CH3,), 3.24 (s, 3H, CH3).

Workup

  1. additionwas slowly added
  2. customthe pyridine evaporated as an azeotrope with toluene

Sources & evidence

ORD record
ord-8417a24b2b694518b67bd1bfce3e1419
Source dataset
uspto-grants-2011_02
Patent number
US07879861B2

Reaction notes

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