HCID 57733272, compound → HCID 67132488, compound

HRID 1920735Notes

Reaction equation

HRID 1920735 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:14]2[C:9](=[C:10]([N+:15]([O-])=O)[CH:11]=[CH:12][CH:13]=2)[C:8](=[O:18])[N:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:6]=1[CH3:25])=[O:4]>C1COCC1.Cl.[Zn]>[CH3:1][O:2][C:3]([C:5]1[C:14]2[C:9](=[C:10]([NH2:15])[CH:11]=[CH:12][CH:13]=2)[C:8](=[O:18])[N:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:6]=1[CH3:25])=[O:4]

Participants

5

Reactant 1

HCID 57733272HCID 57733272, compound

Product 1

HCID 67132488HCID 67132488, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 3-methyl-8-nitro-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid methyl ester (320 mg, 0.95 mmol) and Zn (898 mg, 13.8 mmol) in THF (4.5 ml) and 2M aq. HCl (4.5 ml) was stirred for 10 min, filtered and partitioned between ethyl acetate (3×150 ml) and sat. aq. NaHCO3 (100 ml). The combined organic solution was dried (MgSO4) and evaporated to give 8-amino-3-methyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid methyl ester as a dark oil (200 mg, 0.645 mmol, 69% yield. LC-MS (m/z) 309.4 (MH+); tR=1.2. It was dissolved in conc. aq. HCl (0.4 ml) and H2O (3.25 ml). To the obtained solution NaNO2 (46.3 mg, 0.645 mmol, in 0.12 ml H2O) was added dropwise at 0° C. After 15 min it was neutralized (pH=6-7) with sat. aq. NaHCO3 to give diazonium salt solution. To a solution of KCN (202 mg, 3 mmol) in water (0.4 ml) solution of CuSO4×5H2O (197 mg, 0.774 mmol) in water (0.8 ml) was added dropwise at 0° C. After addition completion benzene (2 ml) was added and the mixture was warmed to +60° C. To this mixture diazonium salt solution was added dropwise during 15 min then kept at 70° C. for 85 min. It was allowed to cool to r.t., diluted with ethyl acetate (10 ml) and filtered via plug of cellite. The organic layer was washed with brine (10 ml), dried (MgSO4) and evaporated to give 97.9 mg of the title compound (48% yield). LC-MS (m/z) 319.2 (MH+); tR=1.15.

Workup

  1. filtrationfiltered
  2. custompartitioned between ethyl acetate (3×150 ml) and sat. aq. NaHCO3 (100 ml)
  3. dry with materialThe combined organic solution was dried (MgSO4)
  4. customevaporated

Sources & evidence

ORD record
ord-efd87835158347849eaacb884950393c
Source dataset
uspto-grants-2012_05
Patent number
US08173639B2

Reaction notes

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