Dichloromethane methanol → 5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 577506Notes

Reaction equation

HRID 577506 reaction equation
C([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[C:19]([Cl:34])[C:20]([C:27]4[N:31]([CH3:32])[N:30]=[N:29][C:28]=4[CH3:33])=[CH:21][C:22]=3[Cl:26])[C:17]2=[O:35])=[C:13]([CH3:36])[CH:12]=[C:11]([CH3:37])[N:10]=1)C1C=CC=CC=1.ClCCl.CO>FC(F)(F)C(O)=O>[Cl:26][C:22]1[CH:21]=[C:20]([C:27]2[N:31]([CH3:32])[N:30]=[N:29][C:28]=2[CH3:33])[C:19]([Cl:34])=[C:18]2[C:23]=1[CH2:24][CH2:25][N:16]([CH2:15][C:14]1[C:9](=[O:8])[NH:10][C:11]([CH3:37])=[CH:12][C:13]=1[CH3:36])[C:17]2=[O:35]

Participants

4

Reactant 2

HCID 21226129Dichloromethane methanolHCID 86723731{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5,8-dichloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867237325,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-oneYield 54.8%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
45 °C

Procedure

A solution of 229a (1.1 g, 2.1 mmol) was dissolved in trifluoroacetic acid (25 mL) and stirred at 45° C. for 3 hours. TLC (dichloromethane/methanol=10:1, Rf: 0.5) showed the reaction was complete. The mixture was concentrated and diluted with dichloromethane (30 mL), washed with aqueous sodium bicarbonate (4×50 mL) and brine (2×20 mL), dried over sodium sulfate, and concentrated to dryness. The residue was purified by flash chromatography (eluting with 10:1 dichloromethane methanol) to afford 5,8-dichloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one (Example 229, 514 mg, 51% yield) as a white solid. 1H NMR (400 MHz, CDCl3): δ 11.73 (s, 1H), 7.31 (s, 1H), 5.95 (s, 1H), 4.77 (s, 2H), 3.85 (s, 3H), 3.77 (t, J=12.8 Hz, 2H), 3.06-3.02 (m, 2H), 2.38 (s, 3H), 2.29 (s, 3H), 2.21 (s, 3H). MS: 446.1 [M+1].

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with dichloromethane (30 mL)
  3. washwashed with aqueous sodium bicarbonate (4×50 mL) and brine (2×20 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated to dryness
  6. customThe residue was purified by flash chromatography (eluting with 10:1 dichloromethane methanol)

Sources & evidence

ORD record
ord-e571f4535793418a9ac7627367e55f71
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

Loading…