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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 1867150
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HRID 1867150 반응식
[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]
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참가 물질

7

반응물 5

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

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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) δ7.85 (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). ESHRMS m/z 546.0987 and 548.1018 (M+H calculated for C25H26BrFN3O5 requires 546.1034 and 548.1018).

후처리

  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%)

출처 및 근거

ORD 기록
ord-890e8d148a6a42988f6e075441941db7
출처 데이터셋
uspto-grants-2009_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07629363B2

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