Phosphoric Acid → HCID 22222230, compound

HRID 1819752Notes

Reaction equation

HRID 1819752 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.Cl.[CH3:18][S:19]([C:22]1[CH:29]=[CH:28][C:25]([CH2:26]N)=[CH:24][CH:23]=1)(=[O:21])=[O:20].C(N(C(C)C)CC)(C)C.P(=O)(O)(O)O>O1CCCC1.CO>[Cl:1][C:2]1[N:11]=[C:10]([CH2:26][C:25]2[CH:24]=[CH:23][C:22]([S:19]([CH3:18])(=[O:21])=[O:20])=[CH:29][CH:28]=2)[C:9]2[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1

Participants

7

Reactant 4

HCID 1004Phosphoric AcidHCID 81531DiisopropylethylamineHCID 5203272,4-Dichloro-6,7-dimethoxyquinazolineHCID 27292694-Methylsulfonylbenzylamine hydrochloride

Product 1

HCID 22222230HCID 22222230, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of commercially available 2,4-dichloro-6,7-dimethoxyquinazoline (200 mg, 0.772 mmol, 1 eq), 4-methylsulfonylbenzylamine hydrochloride (180 mg, 0.810 mmol, 1.05 eq) and diisopropylethylamine (0.40 mL, 2.32 mmol, 3 eq) in tetrahydrofuran (7.7 mL) was heated at reflux for 15.25 h. The reaction mixture was then cooled to rt and concentrated in vacuo. The resultant solid was slurried in methanol (10 mL) collected by filtration, washed with methanol and dried to provide 282 mg (89%) of A1.1 as an off-white solid. LC/MS: 408 [M+H]+; HPLC: 98% at 3.19 min (Phenomenex 5 μm C18 column 4.6×50 mm, 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 254 nm); 1H NMR (400 MHz, DMSO-d6): δ 8.98 (m, 1 H), 7.91 (d, J=8.3 Hz, 2 H), 7.69 (s, 1 H), 7.62 (d, J=8.3 Hz, 2 H), 7.11 (s, 1 H), 4.84 (apparent d, J=5.7 Hz, 2 H), 3.90 (s, 3 H), 3.89 (s, 3 H), 3.19 (s, 3 H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 15.25 h
  3. concentrationconcentrated in vacuo
  4. filtrationcollected by filtration
  5. washwashed with methanol
  6. customdried
  7. customto provide 282 mg (89%) of A1.1 as an off-white solid

Sources & evidence

ORD record
ord-d1f13f5626944a44a3d9a5289cbfad01
Source dataset
uspto-grants-2009_10
Patent number
US07601836B2

Reaction notes

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