HCID 58157157, compound → HCID 53322866, compound

HRID 1921235Notes

Reaction equation

HRID 1921235 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([CH2:12][C:13]1[CH:14]=[C:15]([C:24]([O:26]CC)=[O:25])[C:16](=[O:23])[N:17]3[C:22]=1[CH:21]=[CH:20][CH:19]=[CH:18]3)[CH2:6][CH2:5]2.[CH3:29][Zn]C>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:29][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([CH2:12][C:13]1[CH:14]=[C:15]([C:24]([OH:26])=[O:25])[C:16](=[O:23])[N:17]3[C:22]=1[CH:21]=[CH:20][CH:19]=[CH:18]3)[CH2:6][CH2:5]2

Participants

5

Reactant 2

HCID 58157157HCID 58157157, compoundHCID 178477796HCID 178477796, compound

Product 1

HCID 53322866HCID 53322866, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 1-[(6-bromo-3,4-dihydroisoquinolin-2(1H)-yl)methyl]-4-oxo-4H-quinolizine-3-carboxylate (0.045 g, 0.10 mmol) in 1 mL THF under nitrogen was added 1.0 M dimethylzinc solution in THF (0.112 mL, 0.112 mmol), and tetrakis(triphenylphosphine)palladium (0) (10 mol %). The reaction mixture was stirred at 60° C. for 4 hours, quenched with 1 mL of saturated aqueous ammonium chloride, then cooled to rt and concentrated in vacuo. To a solution of the resultant brown residue in 1 mL DMSO was added saturated aqueous lithium hydroxide (0.3 mL). After 2 hours, the reaction was acidified with 1 N HCl to pH ˜2, filtered and subjected to purification via reverse phase HPLC to provide the title compound which gave a mass ion (ES+) of 349.0. 1H NMR (400 MHz, DMSO) δ 10.07 (br s, 1H), 9.46 (d, J=6.8 Hz, 1H), 8.70 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 8.22-8.19 (m, 1H), 7.76 (t, J=6.6 Hz, 1H), 7.20-6.97 (m, 3H), 4.89 (s, 2H), 4.40-4.34 (m, 2H), 3.76-3.60 (m, 2H), 3.10-3.02 (m, 2H), 2.26 (s, 3H).

Workup

  1. customquenched with 1 mL of saturated aqueous ammonium chloride
  2. temperaturecooled to rt
  3. concentrationconcentrated in vacuo
  4. additionTo a solution of the resultant brown residue in 1 mL DMSO was added saturated aqueous lithium hydroxide (0.3 mL)
  5. waitAfter 2 hours
  6. filtrationfiltered
  7. customsubjected to purification via reverse phase HPLC

Sources & evidence

ORD record
ord-d8e3c3696843470c845e1894ba39d042
Source dataset
uspto-grants-2012_05
Patent number
US08173672B2

Reaction notes

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