1,4-Dimethyl-5-(tributylstannyl)-1H-1,2,3-triazole → {[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

HRID 577505Notes

Reaction equation

HRID 577505 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[C:19]([Cl:28])[C:20](Br)=[CH:21][C:22]=3[Cl:26])[C:17]2=[O:29])=[C:13]([CH3:30])[CH:12]=[C:11]([CH3:31])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:32][N:33]1[C:37]([Sn](CCCC)(CCCC)CCCC)=[C:36]([CH3:51])[N:35]=[N:34]1>[Cu]I.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.O1CCOCC1>[CH2:1]([O:8][C:9]1[C:14]([CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[C:19]([Cl:28])[C:20]([C:37]4[N:33]([CH3:32])[N:34]=[N:35][C:36]=4[CH3:51])=[CH:21][C:22]=3[Cl:26])[C:17]2=[O:29])=[C:13]([CH3:30])[CH:12]=[C:11]([CH3:31])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 578265181,4-Dimethyl-5-(tributylstannyl)-1H-1,2,3-triazoleHCID 867237282-((2-(benzyloxy)-4,6-dimethylpyridin-3-yl)methyl)-7-bromo-5,8-dichloro-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 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)-oneYield 21%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

To a mixture of 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-7-bromo-5,8-dichloro-3,4-dihydroisoquinolin-1(2H)-one (253 g, 500 mg, 0.96 mmol), and 1,4-dimethyl-5-(tributylstannanyl)-1H-1,2,3-triazole (CAS: 1047637-17-1, 754 mg, 1.95 mmol) in a microwave tube was added 1,4-dioxane (10 mL), copper (I) iodide (28 mg, 0.14 mmol) and tetrakis(triphenylphosphine)palladium(0) (160 mg, 0.14 mmol). The solution was degassed using a stream of argon gas and degassing was continued for 10 minutes. The microwave vial was sealed and the mixture was heated at 125° C. for 2 hours under microwave irradiation. TLC (petroleum ether/ethyl acetate=1:1, Rf: 0.5) showed about 50% of 253g remained. However, further heating did not prove fruitful. The mixture was diluted with methyl tert-butyl ether (100 mL), washed with water (3×100 mL), dried over sodium sulfate and concentrated to dryness. The residue was purified by flash chromatography eluting with petroleum ether/ethyl acetate=1:1 to yield -{[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 (229a, 108 mg, 21% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.76 (s, 1H), 7.44 (d, J=1.35 Hz, 2H), 7.28-7.34 (m, 3H), 6.75 (s, 1H), 5.38 (s, 2H), 4.71 (s, 2H), 3.77 (s, 3H), 3.30-3.34 (m, 2H), 2.82 (s, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 2.08 (s, 3H) MS: 446.1 [M+1].

Workup

  1. customThe solution was degassed
  2. customdegassing
  3. customThe microwave vial was sealed
  4. temperatureHowever, further heating
  5. additionThe mixture was diluted with methyl tert-butyl ether (100 mL)
  6. washwashed with water (3×100 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by flash chromatography
  10. washeluting with petroleum ether/ethyl acetate=1:1

Sources & evidence

ORD record
ord-338222fea22e444a9262e82a973ee9d5
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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