Tetrahydrofuran → HCID 23061000, compound

HRID 750347Notes

Reaction equation

HRID 750347 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([Cl:20])[CH:18]=3)[C:13](=[O:21])[N:12]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[C:11]=2[C:33](=[O:36])[CH2:34][CH3:35])=[CH:6][CH:5]=1.[CH2:38]1COCC1>ClCCl>[C:3]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([Cl:20])[CH:18]=3)[C:13](=[O:21])[N:12]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[C:11]=2[C:33](=[O:36])[CH2:34][CH3:35])=[CH:8][CH:9]=1)(=[O:2])[CH3:38]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 69156846HCID 69156846, compound

Product 1

HCID 23061000HCID 23061000, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution (2.0 ml) of 4-[6-chloro-2-(4-methanesulfonylbenzyl)-1-oxo-3-propionyl-1,2-dihydroisoquinolin-4-yl]benzoic acid methyl ester (100 mg) in THF was added dropwise gently a methyl lithium diethyl ether solution (1.1 mol/l, 0.25 ml) at −50° C. with stirring, and the mixture was allowed to warm to room temperature and stirred for 18 hrs. The reaction mixture was diluted with dichloromethane, washed with 1N hydrochloric acid, and the organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (9 mg) in beige crystals. 1H NMR (CDCl3) δ: 0.54 (3H, t, J=7.2 Hz), 1.78 (2H, q, J=7.2 Hz), 2.67 (3H, s), 3.02 (3H, s), 5.35 (2H, s), 7.19 (1H, d, J=2.1 Hz), 7.37-7.47 (4H, m), 7.54 (1H, dd, J=2.1 Hz), 7.89 (2H, d, J=8.7 Hz), 8.06 (2H, d, J=8.7 Hz), 8.47 (1H, d, J=8.7 Hz). HPLC analysis: purity 97.7% (retention time: 4.29 min). MS (ESI+): 522.0 (M+H), 524.0.

Workup

  1. stirringstirred for 18 hrs
  2. washwashed with 1N hydrochloric acid
  3. dry with materialthe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-0cc497eb50be43b483e1ed7263c1acaf
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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