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

HRID 69422Notes

Reaction equation

HRID 69422 reaction equation
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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

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

Conditions

Temperature
50 °C

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-1781d5c5563a47a398986bd54da62b43
Source dataset
uspto-grants-2014_09
Patent number
US08822495B2

Reaction notes

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