Methyl iodide → HCID 58681878, compound

HRID 10309Notes

Reaction equation

HRID 10309 reaction equation
[C:1]([O:5][C:6](=[O:39])[NH:7][N:8]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]([Cl:34])[C:13]([N:20]3[CH2:24][CH2:23][C@H:22]([N:25]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH3:26])[CH2:21]3)=[C:14]([F:19])[CH:15]=2)[N:10]([CH:35]2[CH2:37][CH2:36]2)[C:9]1=[O:38])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:43]>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:39])[N:7]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]([Cl:34])[C:13]([N:20]3[CH2:24][CH2:23][C@H:22]([N:25]([C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])[CH3:26])[CH2:21]3)=[C:14]([F:19])[CH:15]=2)[N:10]([CH:35]2[CH2:36][CH2:37]2)[C:9]1=[O:38])[CH3:43])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69068551HCID 69068551, compound

Product 1

HCID 58681878HCID 58681878, compoundYield 48.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of {7-[(S)-3-(tert-butoxycarbonyl-N-methylamino)-pyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}carbamic acid tert-butyl ester from Example 8 (0.238 g, 0.421 mmol) in N,N-dimethylformamide (5 mL) at −78° C. under nitrogen atmosphere is added sodium hydride (60% dispersion in mineral oil, 0.025 g, 0.631 mmol). After 30 minutes, iodomethane (0.052 mL, 0.842 mmol) is added, and the reaction mixture is warmed to room temperature. After 1 hour, the reaction mixture is diluted with ethyl acetate and washed with saturated ammonium chloride solution, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate concentrated. The resulting residue is purified by flash column chromatography (1:1 ethyl acetate/hexanes) to afford the title compound (0.118 g). 1H NMR (CDCl3): δ 7.63 (dd, 1H), 4.78 (bs, 1H), 3.87–3.45 (m, 6H), 2.62–2.44 (m, 6H), 2.31–2.12 (m, 2H), 1.49–1.47 (m, 18H), 1.23–1.07 (m, 2H), 0.75–0.53 (m, 2H). MS CI: m/z 582 (MH+).

Workup

  1. waitAfter 1 hour
  2. washwashed with saturated ammonium chloride solution, water, and brine
  3. dry with materialThe organic layer is dried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated
  6. customThe resulting residue is purified by flash column chromatography (1:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-47358ccb45f14dbb802e1a7480724754
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

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