Methyl iodide → Ethyl 4-(4-aminophenoxy)-2-aminopyridin-3-yl-methyl-carbamate

HRID 1864663Notes

Reaction equation

[NH2:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[C:8]=2[NH:14][C:15](=[O:19])[O:16][CH2:17][CH3:18])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:24]I>C1COCC1>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[C:8]=2[N:14]([CH3:24])[C:15](=[O:19])[O:16][CH2:17][CH3:18])=[CH:20][CH:21]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Method O1. Ethyl 4-(4-aminophenoxy)-2-aminopyridin-3-yl-carbamate (72 mg, 0.25 mmol) was dissolved in dry THF (3 mL) and cooled at 0° C. Sodium hydride (11 mg, 0.28 mmol) was added, and the reaction mixture was stirred for 25 minutes. Methyl iodide (18 μL, 0.25 mmol) was added. The mixture was stirred at 0° C. for 30 minutes and at room temperature for 1.5 hours. The solvent was evaporated and the residue extracted between DCM and saturated Na2CO3. The organic layer was dried and evaporated, and the residue purified by column chromatography (eluent AcOEt) to afford the title compound (40 mg, 53%). 1H-NMR (δ, ppm, DMSO-d6): 1.10 (t, 3H, CH3,Et, J=7.04 Hz), 3.01 (s, 3H, CH3N), 3.90-4.10 (m, 2H, CH2,Et), 5.06 (s, 2H, NH2,Ph), 5.78 (d, 1H, HPy,5, J=6.68 Hz), 5.97 (s, 2H, NH2,Py2), 6.59 (d, 2H, Harom,Ph,3+5, J=8.76 Hz), 6.73 (d, 2H, Harom,Ph,2+6, J=8.79 Hz), 7.67 (d, 1H, HPy,6, J=5.73 Hz). LC-MS (m/z): 302 (M+, 100). Acc. mass (C15H19N4O3): calculated 303.1457, found 303.1453.

Workup

stirringThe mixture was stirred at 0° C. for 30 minutes and at room temperature for 1.5 hours
customThe solvent was evaporated
extractionthe residue extracted between DCM and saturated Na2CO3
customThe organic layer was dried
customevaporated
customthe residue purified by column chromatography (eluent AcOEt)

Sources & evidence

ORD record: ord-fce6cf9ca5a341f5a425f32e1ef35149
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07625922B2

Reaction notes

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