Propionic Acid → (Rac)-Baxdrostat

HRID 530346ノート

反応式

HRID 530346 の反応式
[NH2:1][CH:2]1[C:11]2[CH:10]=[N:9][CH:8]=[C:7]([C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]([CH3:22])[C:17](=[O:23])[CH2:16][CH2:15]4)[C:6]=2[CH2:5][CH2:4][CH2:3]1.[C:24](O)(=[O:27])[CH2:25][CH3:26].CCN=C=NCCCN(C)C.OP([O-])(O)=O.[K+]>C(Cl)Cl>[CH3:22][N:18]1[C:19]2[C:14](=[CH:13][C:12]([C:7]3[C:6]4[CH2:5][CH2:4][CH2:3][CH:2]([NH:1][C:24](=[O:27])[CH2:25][CH3:26])[C:11]=4[CH:10]=[N:9][CH:8]=3)=[CH:21][CH:20]=2)[CH2:15][CH2:16][C:17]1=[O:23]

参加物

6

反応物 4

HCID 1032Propionic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 516951Monobasic potassium phosphateHCID 71538469Baxdrostat Impurity 30

生成物 1

HCID 71535961(Rac)-Baxdrostat収率 101.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a stirred brown solution of (rac)-6-(8-amino-5,6,7,8-tetrahydroisoquinolin-4-yl)-1-methyl-3,4-dihydroquinolin-2(1H)-one (intermediate A-2) (92.2 mg, 0.30 mmol) and propionic acid (24.4 mg, 0.33 mmol) in CH2Cl2 (1.5 mL) at 0° C. under Argon was added EDCI (63.3 mg, 0.33 mmol). Stirring was continued over night and the reaction mixture was allowed to warm up to room temperature. The reaction mixture was poured into aq. 10% KH2PO4 solution followed by extraction with AcOEt (3×). The organic phases were washed once with aq. 10% KH2PO4, aq. sat. NaHCO3 and with aq. sat. NaCl solution; the combined organic phases were dried over Na2SO4, filtered and evaporated to afford the title compound (111 mg, quantitative) as light yellow foam. MS: 364.2 (M+H+).

後処理

  1. waitwas continued over night
  2. extractionfollowed by extraction with AcOEt (3×)
  3. washThe organic phases were washed once with aq. 10% KH2PO4, aq. sat. NaHCO3 and with aq. sat. NaCl solution
  4. dry with materialthe combined organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated

出典と根拠

ORDレコード
ord-b36019ef057240a89eecd18994011de7
出典データセット
uspto-grants-2016_05
特許番号
US09353081B2

反応ノート

読み込み中…