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

HRID 711091ノート

反応式

HRID 711091 の反応式
[CH3:1][NH2:2].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>>[CH3:1][NH:2][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

参加物

4

反応物 3

HCID 6329Methylamine2 回HCID 8028TetrahydrofuranHCID 86664617Ethyl 1-chloroisoquinoline-7-carboxylate2 回

生成物 1

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

反応条件

温度
60 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-3f2692551b794c06a02ca592241826fd
出典データセット
uspto-grants-2015_11
特許番号
US09181252B2

反応ノート

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