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

HRID 69422노트

반응식

HRID 69422 반응식
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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

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

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온도
50 °C

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-1781d5c5563a47a398986bd54da62b43
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822495B2

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