Sodium Hydroxide → 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid {(S)-2-[3-(4-methoxy-phenyl)-propylamino]-pentyl}-amide hydrochloride

HRID 1183025ノート

反応式

HRID 1183025 の反応式
Cl.[NH2:2][C@@H:3]([CH2:17][CH2:18][CH3:19])[CH2:4][NH:5][C:6]([C:8]1[C:13]([NH2:14])=[N:12][C:11]([NH2:15])=[C:10]([Cl:16])[N:9]=1)=[O:7].[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][CH:30]=O)=[CH:24][CH:23]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C(Cl)Cl>[ClH:16].[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][CH2:30][NH:2][C@@H:3]([CH2:17][CH2:18][CH3:19])[CH2:4][NH:5][C:6]([C:8]2[C:13]([NH2:14])=[N:12][C:11]([NH2:15])=[C:10]([Cl:16])[N:9]=2)=[O:7])=[CH:24][CH:23]=1

参加物

6

反応物 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 111266073-(4-Methoxyphenyl)propanalHCID 866518883,5-Diamino-6-chloro-pyrazine-2-carboxylic acid ((S)-2-amino-pentyl)-amide hydrochloride

生成物 1

HCID 866518933,5-Diamino-6-chloro-pyrazine-2-carboxylic acid {(S)-2-[3-(4-methoxy-phenyl)-propylamino]-pentyl}-amide hydrochloride

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid ((S)-2-amino-pentyl)-amide hydrochloride (Example 4) (400 mg, 1.467 mmol), 3-(4-methoxyphenyl)propionaldehyde (181 mg, 1.103 mmol) and sodium triacetoxyborohydride (467 mg, 2.205 mmol) in DCM (150 mL) is heated at reflux overnight. The reaction mixture is allowed to cool, and 1 N NaOH solution (50 mL) and DCM (50 mL) are added. The organic phase is separated and the aqueous phase is extracted once with DCM. The combined organic phases are washed with sat. aq. NaCl solution, dried (MgSO4), and concentrated in vacuo to afford a yellow solid. Purification by flash column chromatography (SiO2, MeOH:DCM, gradient 2-10%+0.1% TEA) affords the title compound. [M+H]+ 421. 1H NMR (400 MHz, CDCl3) δ 8.69 (2H, br), 8.23 (1H, t), 7.25 (4H, br), 7.11 (2H, d), 6.84 (2H, d), 3.72 (3H, s), 3.55-3.45 (2H, m), 3.25-3.15 (1H, m), 3.03-2.92 (2H, m), 2.58 (2H, t), 1.85-1.73 (2H, m), 1.65-1.27 (4H, m), 0.89 (3H, t).

後処理

  1. temperatureat reflux overnight
  2. temperatureto cool
  3. customThe organic phase is separated
  4. extractionthe aqueous phase is extracted once with DCM
  5. washThe combined organic phases are washed with sat. aq. NaCl solution
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto afford a yellow solid
  9. customPurification by flash column chromatography (SiO2, MeOH:DCM, gradient 2-10%+0.1% TEA)

出典と根拠

ORDレコード
ord-39fbad91bee14dbb8805ec8c09d0f02c
出典データセット
uspto-grants-2014_03
特許番号
US08664228B2

反応ノート

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