Formaldehyde → HCID 57802820, compound

HRID 1752363Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH:24]4[O:29][CH2:28][CH2:27][NH:26][CH2:25]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH2:30]=O>C(O)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH:24]4[O:29][CH2:28][CH2:27][N:26]([CH3:30])[CH2:25]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(morpholin-2-ylmethyl)oxy]quinazolin-4-amine (3.32 g, 7.7 mmol) in formic acid (33.2 mL) was added a 37 wt % solution of formaldehyde in water (3.32 mL), and the reaction mixture was heated at 95° C. for 2.5 h. After cooling to room temperature, the reaction mixture was concentrated. The residue was dissolved in methanol and treated with Bio-Rad AG®1-X8 hydroxide form resin until pH 8. Filtration and concentration in vacuo afforded 3.11 g (91%) of the title compound as a yellow-brown solid. 1H NMR (400 MHz, d4-MeOH): 8.46 (s, 1H), 8.14 (d, 1H), 7.73 (dd, 1H), 7.68 (s, 1H), 7.48 (d, 1H), 7.13 (s, 1H), 4.21-4.09 (m, 2H), 4.02 (s, 3H), 4.01-3.91 (m, 3H), 2.96 (m, 1H), 2.75 (m, 1H), 2.35 (s, 3H), 2.22 (m, 1H), 2.11 (t, 1H); MS (EI) for C21H22N4O3Cl2: 449 (MH+).

Workup

temperatureAfter cooling to room temperature
concentrationthe reaction mixture was concentrated
dissolutionThe residue was dissolved in methanol
additiontreated with Bio-Rad AG®1-X8 hydroxide form resin until pH 8
filtrationFiltration and concentration in vacuo

Sources & evidence

ORD record: ord-847abfb16a92472e8b477b3e4d20a2bc
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163006B2

Reaction notes

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