Methyl iodide → N-(4-Fluoro-2-(1-methyl-1H-pyrazol-3-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

HRID 1372331Notes

Reaction equation

HRID 1372331 reaction equation
[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[N:17]([C:18](=[O:28])[C:19]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:16][CH2:15][O:14][C:13]3([CH3:30])[CH3:29])=[O:9])=[C:4]([C:33]2[NH:37][N:36]=[CH:35][CH:34]=2)[CH:3]=1.IC.[C:40](=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[N:17]([C:18](=[O:28])[C:19]=2[O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:16][CH2:15][O:14][C:13]3([CH3:30])[CH3:29])=[O:9])=[C:4]([C:33]2[CH:34]=[CH:35][N:36]([CH3:40])[N:37]=2)[CH:3]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 21069996HCID 21069996, compound

Product 1

HCID 21069997N-(4-Fluoro-2-(1-methyl-1H-pyrazol-3-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamideYield 64.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of N-(4-fluoro-2-(1H-pyrazol-5-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.185 g, 0.36 mmol) in N,N-dimethylformamide (3 ml) was treated with iodomethane (0.025 ml, 0.4 mmol) and potassium carbonate (0.076 g, 0.55 mmol) and the resulting mixture was stirred at 25° C. for 5 h. The reaction mixture was then diluted with ethyl acetate, washed with water, brine, dried over anhydrous magnesium and concentrated. Chromatography of the residue on silica gel (elution gradient of ethyl acetate in dichloromethane) gave 0.120 g (64% yield) of the title compound as a white solid. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.62 (6H, s, 2×CH3), 3.84 (3H, s, NCH3), 3.95–4.05 (4H, m, 2×CH2), 4.69 (2H, d, J=6.1 Hz, NCH2), 5.21 (2H, s, OCH2), 6.49 (1H, d, J=2.2 Hz, CH), 7.01 (1H, m, aromatic), 7.24–7.3 (4H, m, aromatics), 7.40 (1H, d, J=2.2 Hz, CH), 7.42–7.45 (2H, m, aromatics), 7.64 (1H, dd, J=6.1 Hz and J=8.6 Hz, aromatic), 8.75 (1H, broad t, NH). HRMS (ESI+) calculated for C28H29FN5O4 [M+H+]: 518.2204. found: 518.2222.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over anhydrous magnesium
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-874e711c42b046ad882549e623fe6eaf
Source dataset
uspto-grants-2007_01
Patent number
US07157447B2

Reaction notes

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