Methanol → 2-[4-((R)-3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid methyl ester

HRID 69422ノート

反応式

HRID 69422 の反応式
C(N(CC)CC)C.[CH3:8][N:9]([CH3:41])[C@@H:10]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:30][CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[C:26](OS(C(F)(F)F)(=O)=O)[CH:27]=4)[C:22]3=[O:39])=[CH:17][C:16]=2[F:40])[CH2:11]1.CN([CH:45]=[O:46])C.[CH3:47][OH:48]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:47][O:48][C:45]([C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][CH:25]=1)[C:22](=[O:39])[N:21]([C:18]1[CH:19]=[CH:20][C:15]([N:12]3[CH2:13][CH2:14][C@@H:10]([N:9]([CH3:41])[CH3:8])[CH2:11]3)=[C:16]([F:40])[CH:17]=1)[CH2:30][CH2:29]2)=[O:46]

参加物

6

反応物 4

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 86635103Trifluoromethanesulfonic acid 2-[4-((R)-3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl ester

生成物 1

HCID 689906132-[4-((R)-3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid methyl ester

試薬・触媒・溶媒 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒

反応条件

温度
50 °C

実験手順

Triethylamine (1.0 g) and then Pd(dppf)Cl2 (365 mg) were added to a mixture of trifluoromethanesulfonic acid 2-[4-((R)-3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl ester (2.5 g), DMF (50 mL) and methanol (25 mL). The mixture was heated at 50° C. in an autoclave under a CO atmosphere (5 bar) for 6 hours. The cooled and decompressed reaction mixture was partitioned between water and ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by preparative HPLC. The product with the molecular weight of 411.48 (C23H26FN3O3) was obtained in this way; MS (ESI): 412 (M+H+).

後処理

  1. temperatureThe cooled
  2. customreaction mixture
  3. customwas partitioned between water and ethyl acetate
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC
  7. customThe product with the molecular weight of 411.48 (C23H26FN3O3) was obtained in this way

出典と根拠

ORDレコード
ord-1781d5c5563a47a398986bd54da62b43
出典データセット
uspto-grants-2014_09
特許番号
US08822495B2

反応ノート

読み込み中…