Methylamine → Methyl 2-{[(3-bromo-6-methyl-1-{2-methyl-5-[(methylamino)carbonyl]phenyl}-2-oxo-1,2-dihydropyridin-4-yl)oxy]methyl}-5-fluorobenzylcarbamate

HRID 1832105Notes

Reaction equation

HRID 1832105 reaction equation
[Br:1][C:2]1[C:3](=[O:34])[N:4]([C:24]2[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=2[CH3:33])[C:27](O)=[O:28])[C:5]([CH3:23])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[CH2:17][NH:18][C:19]([O:21][CH3:22])=[O:20].ClC(OCC(C)C)=O.[CH3:43][N:44]1CCOCC1.CN.C1COCC1>CN(C=O)C>[Br:1][C:2]1[C:3](=[O:34])[N:4]([C:24]2[CH:25]=[C:26]([C:27]([NH:44][CH3:43])=[O:28])[CH:30]=[CH:31][C:32]=2[CH3:33])[C:5]([CH3:23])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[CH2:17][NH:18][C:19](=[O:20])[O:21][CH3:22]

Participants

7

Reactant 5

HCID 6329MethylamineHCID 79724-MethylmorpholineHCID 8028TetrahydrofuranHCID 62365Isobutyl chloroformateHCID 22050291HCID 22050291, compound

Product 1

HCID 21035364Methyl 2-{[(3-bromo-6-methyl-1-{2-methyl-5-[(methylamino)carbonyl]phenyl}-2-oxo-1,2-dihydropyridin-4-yl)oxy]methyl}-5-fluorobenzylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled (−10° C.) solution of 3-[3-bromo-4-[(4-fluoro-2-{[(methoxycarbonyl)amino]methyl}benzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoic acid (0.07 g, 0.13 mmol) in DMF (2.0 mL) was added isobutyl chloroformate (0.02 mL, 0.16 mmol) and 4-methylmorpholine (0.02 mL, 0.16 mmol). After 15 min, 2.0M methylamine in THF (0.01 mL, 0.20 mmol) was added. Solvent removed by distillation after 30 min. Crude product purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO3 (30 mL) and extracted in DCM (3×25 mL). The organic extracts were dried over Na2SO4, filtered, concentrated, and dried in vacuo to give a white foam, (0.061 g, 86%). 1H NMR (CD3OD/400 MHz) δ 7.85 (m, 1H), 7.54 (m, 3H), 7.14 (m, 1H), 7.05 (m, 1H), 6.68 (s, 1H), 5.40 (s, 2H), 4.43 (s, 2H), 3.64 (s, 3H), 2.89 (s, 3H), 2.08 (s, 3H), 1.99 (s, 3H). ES HRMS m/z 546.0987 and 548.1018 (M+H calculated for C25H26BrFN3O5 requires 546.1034 and 548.1018).

Workup

  1. customSolvent removed by distillation after 30 min
  2. customCrude product purified by preparatory HPLC
  3. customAcetonitrile was evaporated
  4. washthe solution washed with 5% NaHCO3 (30 mL)
  5. extractionextracted in DCM (3×25 mL)
  6. dry with materialThe organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customdried in vacuo
  10. customto give a white foam, (0.061 g, 86%)

Sources & evidence

ORD record
ord-d8df37dffc724521a83edc0cd727b42b
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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