Triethylamine → 4-[3-Oxo-7-(3-phenyl-prop-1-ynyl)-2H-isoquinolin-2-ylmethyl]benzoic Acid tert-butyl Ester

HRID 488773Notes

Reaction equation

HRID 488773 reaction equation
[C:1]([O:5][C:6](=[O:26])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][N:14]2[C:23](=[O:24])[CH:22]=[C:21]3[C:16]([CH:17]=[C:18](Br)[CH:19]=[CH:20]3)=[CH:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:34]1([CH2:40][C:41]#[CH:42])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CN(C)C=O.[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>[C:1]([O:5][C:6](=[O:26])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][N:14]2[C:23](=[O:24])[CH:22]=[C:21]3[C:16]([CH:17]=[C:18]([C:42]#[C:41][CH2:40][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH:19]=[CH:20]3)=[CH:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 575753BenzylacetyleneHCID 865911974-(7-bromo-3-oxo-2H-isoquinolin-2-ylmethyl)benzoic acid tert-butyl ester

Product 1

HCID 99334174-[3-Oxo-7-(3-phenyl-prop-1-ynyl)-2H-isoquinolin-2-ylmethyl]benzoic Acid tert-butyl Ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A solution of 4-(7-bromo-3-oxo-2H-isoquinolin-2-ylmethyl)benzoic acid tert-butyl ester (1.50 g, 3.62 mmol) in dimethylformamide (10 mL) is degassed with nitrogen, then treated with triethyl-amine (2.07 mL, 14.8 mmol), CuI (0.050 g, 0.26 mmol), Pd(Ph3P)4 (0.173 g, 0.15 mmol), and 3-phenyl-1-propyne (1.13 mL, 9.05 mmol). The reaction mixture is heated in an oil bath at 65° C. for 5 hours, cooled to room temperature, the DMF is evaporated, and the residue is dissolved in ethyl acetate. The solution is washed with 1N HCl, brine, dried over MgSO4 and evaporated onto silica gel. Purification on a 3.5×18 cm silica gel column eluted with hexane/ethyl acetate 4:1, followed by drying, will afford the desired product.

Workup

  1. temperaturecooled to room temperature
  2. customthe DMF is evaporated
  3. dissolutionthe residue is dissolved in ethyl acetate
  4. washThe solution is washed with 1N HCl, brine
  5. dry with materialdried over MgSO4
  6. customevaporated onto silica gel
  7. customPurification on a 3.5×18 cm silica gel column
  8. washeluted with hexane/ethyl acetate 4:1
  9. customby drying

Sources & evidence

ORD record
ord-26f8241dba4e4706b8e6ca72391269e1
Source dataset
uspto-grants-2005_12
Patent number
US06974822B2

Reaction notes

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