Methylamine → Ethyl 1-(methylamino)isoquinoline-7-carboxylate

HRID 880975노트

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HRID 880975 반응식
CN.O1CCCC1.Cl[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:17]=2)[CH:12]=[CH:11][N:10]=1.COC1C=CC([CH2:30][NH:31]C2C3C(=CC=C(C(O)=O)C=3)C=CN=2)=CC=1>>[CH3:30][NH:31][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:17]=2)[CH:12]=[CH:11][N:10]=1

참가 물질

5

반응물 4

HCID 6329Methylamine2회HCID 8028TetrahydrofuranHCID 674916931-(4-Methoxybenzylamino)isoquinoline-7-carboxylic acidHCID 86664617Ethyl 1-chloroisoquinoline-7-carboxylate

생성물 1

HCID 67491404Ethyl 1-(methylamino)isoquinoline-7-carboxylate수율 85%

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온도
60 °C

실험 절차

A solution of methylamine in tetrahydrofuran (30 mL, 60 mmol, 2 M) was added to ethyl 1-chloroisoquinoline-7-carboxylate (formed in Step 3 of Intermediate 27) (705 mg, 2.99 mmol) in a sealed tube. The reaction was heated to 60° C. and stirred overnight. LCMS indicated the reaction was not complete. Additional methylamine (10 mL, 20 mmol, 2 M in THF) was added and the reaction was heated to 60° C. for another 18 hours. The reaction was cooled to room temperature and concentrated. The residue was partitioned between water and dichloromethane. The organic layer was dried over magnesium sulphate, filtered, and concentrated. Purification by flash column chromatography (25-65% ethyl acetate/heptanes) gave the title compound (584 mg, 85%) as a yellow oil that solidified upon standing. +ESI (M+H) 231.1; 1H NMR (400 MHz, DMSO-d6, δ): 8.83-8.94 (m, 1H), 8.07 (dd, J=8.58, 1.56 Hz, 1H), 7.99 (d, J=5.85 Hz, 1H), 7.89 (d, J=4.49 Hz, 1H), 7.77 (d, J=8.58 Hz, 1H), 6.92 (d, J=5.07 Hz, 1H), 4.38 (q, J=7.02 Hz, 2H), 2.97 (d, J=4.49 Hz, 3H), 1.38 (t, J=7.12 Hz, 3H).

후처리

  1. temperaturethe reaction was heated to 60° C. for another 18 hours
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated
  4. customThe residue was partitioned between water and dichloromethane
  5. dry with materialThe organic layer was dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash column chromatography (25-65% ethyl acetate/heptanes)

출처 및 근거

ORD 기록
ord-84cec0cd5590481687db87a8606afd11
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993586B2

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