Diisopropylethylamine → (E)-6-{2-[methyl-(3-methyl-benzo[b]thiophen-2-ylmethyl)carbamoyl]vinyl}-2-oxo-1,2-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester

HRID 1362309노트

반응식

HRID 1362309 반응식
[CH3:1][N:2]([CH2:7][C:8]1[S:12][C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[C:9]=1[CH3:17])[C:3](=[O:6])[CH:4]=[CH2:5].[CH2:18]([O:20][C:21]([C:23]1[C:24](=[O:34])[NH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][C:29](Br)=[CH:28][N:27]=2)=[O:22])[CH3:19].CCN(C(C)C)C(C)C>C(C#N)C.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:18]([O:20][C:21]([C:23]1[C:24](=[O:34])[NH:25][C:26]2[C:31]([CH:32]=1)=[CH:30][C:29](/[CH:5]=[CH:4]/[C:3](=[O:6])[N:2]([CH3:1])[CH2:7][C:8]1[S:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[C:9]=1[CH3:17])=[CH:28][N:27]=2)=[O:22])[CH3:19]

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 17930139N-methyl-N-(3-methyl-benzo[b]thiophen-2-ylmethyl)acrylamideHCID 53396436Ethyl 6-bromo-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate

생성물 1

HCID 59277530(E)-6-{2-[methyl-(3-methyl-benzo[b]thiophen-2-ylmethyl)carbamoyl]vinyl}-2-oxo-1,2-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester수율 56.3%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매HCID 7854Propionitrile용매

실험 절차

A suspension of N-methyl-N-(3-methyl-benzo[b]thiophen-2-ylmethyl)acrylamide (500 mg, 2.04 mmol), 6-bromo-2-oxo-1,2-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester (665 mg, 2.24 mmol), (o-tol)3P (135 mg, 0.44 mmol) and DIEA (0.4 mL, 2.45 mmol) in EtCN (10 mL) and DMF (10 mL) was deoxygenated with argon for 30 min. Pd(OAc)2 (50 mg, 0.22 mmol) was added, the mixture was deoxygenated with argon for 20 min and then heated to reflux overnight. The mixture was cooled to room temperature and concentrated. The residue was partitioned between CH2Cl2 and H2O. The organic layer was washed with satd NaCl, dried (Na2SO4) and concentrated. Purification by column chromatography (silica gel, 89:10:1 CH2Cl2/MeOH/conc NH4OH) gave the title compound (530 mg, 56%) as a yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 12.63 (s, 1H), 8.98 (d, J=2.1 Hz, 1H), 8.67 (s, 1H), 8.44-8.42 (m, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.75-7.52 (m, 2H), 7.43-7.31 (m, 3H), 5.14-4.91 (m, 2H), 4.32-4.25 (m, 2H), 3.18-2.96 (m, 3H), 2.43 (s, 3H), 1.33-1.27 (m, 3H); MS (ESI) m/e 462 (M+H)+.

후처리

  1. customwas deoxygenated with argon for 30 min
  2. customthe mixture was deoxygenated with argon for 20 min
  3. temperatureheated
  4. temperatureto reflux overnight
  5. concentrationconcentrated
  6. customThe residue was partitioned between CH2Cl2 and H2O
  7. washThe organic layer was washed with satd NaCl
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification by column chromatography (silica gel, 89:10:1 CH2Cl2/MeOH/conc NH4OH)

출처 및 근거

ORD 기록
ord-fd1a798563554238b62ed7c551547be2
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07879872B2

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