Methyl iodide → (2-chloro-quinazolin-4-yl)-(6-methoxy-pyridin-3-yl)-methylamine

HRID 1876085Notes

Reaction equation

[Cl:1][C:2]1[N:11]=[C:10]([NH:12][C:13]2[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:21]I.[H-].[Na+]>CN(C=O)C>[Cl:1][C:2]1[N:11]=[C:10]([N:12]([C:13]2[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[CH3:21])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (2-chloro-quinazolin-4-yl)-(6-methoxy-pyridin-3-yl)-amine (19.4 mg, 0.068 mmol) in 1 mL of DMF cooled at 0° C. was added methyl iodide (100 uL, 1.61 mmol), followed by sodium hydride (60% oil suspension, 5 mg, 0.13 mmol). The mixture was stirred at 0° C. for 1 h, then allowed to warm to room temperature and stirred for 1 h. The reaction mixture was quenched by adding 50 uL of water, diluted with 25 mL of ethyl acetate, washed with water (25 mL×3), saturated NaCl, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by chromatography (20% ethyl acetate/hexanes) to give the title compound (14.3 mg, 0.048 mmol, 70%). 1H NMR (CDCl3) 8.06 (d, J=2.7 Hz, 1H), 7.57-7.79 (m, 1H), 7.60 (ddd, J=8.1, 6.6 and 1.2 Hz, 1H), 7.44 (dd, J=8.7 and 2.7 Hz, 1H), 7.09 (ddd, J=8.1, 6.6 and 1.2 Hz, 1H), 6.99-7.02 (m, 1H), 6.82 (dd, J=8.7 and 0.6 Hz, 1H), 3.97 (s, 3H), 3.61 (s, 3H).

Workup

temperatureto warm to room temperature
stirringstirred for 1 h
customThe reaction mixture was quenched
additionby adding 50 uL of water
additiondiluted with 25 mL of ethyl acetate
washwashed with water (25 mL×3), saturated NaCl
dry with materialdried over anhydrous MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by chromatography (20% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-45f7c19fcd5d4d5b9be35575023e0fb5
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08309562B2

Reaction notes

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