(3R)-3-amino-3-phenylpropanoic acid → (R)-3-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-3-phenyl-propionic acid

HRID 1481028

반응식

HRID 1481028 반응식
[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=2)[C:6]([OH:20])=[C:5]([C:21](OC)=[O:22])[N:4]=1)#[N:2].[NH2:25][C@@H:26]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:27][C:28]([OH:30])=[O:29].C[O-].[Na+]>COCCO>[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=2)[C:6]([OH:20])=[C:5]([C:21]([NH:25][C@@H:26]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:27][C:28]([OH:30])=[O:29])=[O:22])[N:4]=1)#[N:2]

참가 물질

5

반응물 3

HCID 686703(3R)-3-amino-3-phenylpropanoic acidHCID 10942334Sodium MethoxideHCID 89812860HCID 89812860, 화합물

생성물 1

HCID 71737525(R)-3-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-3-phenyl-propionic acid

시약·촉매·용매 1

HCID 80192-Methoxyethanol용매

실험 절차

Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate (20 mg, 0.06 mmol), (R)-3-amino-3-phenyl-propionic acid (62 mg, 0.38 mmol, PepTech) and sodium methoxide (19 mg, 0.35 mmol) were suspended in 2-methoxyethanol (3 mL). The resulting mixture was heated to reflux for 3 hours and then cooled to room temperature. The solvent was removed in vacuo and the residue was dissolved in H2O (15 mL) and EtOAc (15 mL). To the stirred mixture was added 1 N hydrochloric acid until pH was 1. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-50% EtOAc/CH2Cl2 with 0.5% formic acid) to give the title compound in 17 mg. MS: (−) m/z 451.93 (M−1).

후처리

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 3 hours
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in H2O (15 mL)
  5. additionTo the stirred mixture was added 1 N hydrochloric acid until pH was 1
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted twice with EtOAc
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. concentrationconcentrated
  10. custompurified by flash chromatography (0-50% EtOAc/CH2Cl2 with 0.5% formic acid)

출처 및 근거

ORD 기록
ord-11613c29fc154c42b7661b7bd0258354
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409892B2

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