Triethylamine → HCID 10389390, compound

HRID 915374Notes

Reaction equation

HRID 915374 reaction equation
[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)=[CH:13][C:12]2[C:7](=[CH:8][C:9]([F:22])=[CH:10][CH:11]=2)[C:6]1=[O:23].[C:29]1(B(O)O)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(N(CC)CC)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:14]([C:15]2[CH:16]=[CH:17][C:18]([O:21][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:19][CH:20]=2)=[CH:13][C:12]2[C:7](=[CH:8][C:9]([F:22])=[CH:10][CH:11]=2)[C:6]1=[O:23]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 66827Phenylboronic AcidHCID 66884416HCID 66884416, compound

Product 1

HCID 10389390HCID 10389390, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(2,4-difluorobenzyl)-7-fluoro-3-(4-hydroxyphenyl)-2H-isoquinolin-1-one (54 mg, 0.14 mmol), a compound of formula (Id), in CH2Cl2 (8 mL) was added phenylboronic acid (35 mg, 0.28 mmol), copper (II) acetate (51 mg, 0.28 mmol), and powdered activated 4 Å molecular sieves (500 mg). The mixture was stirred for 10 minutes then treated with triethylamine (99 μL, 0.71 mmol). The resulting suspension was stirred for 72 hours at ambient temperature. The mixture was then filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by preparative thin-layer chromatography on silica gel eluting with 25% EtOAc/hexanes to afford 2-(2,4-difluorobenzyl)-7-fluoro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one, a compound of formula (Id), (29 mg, 45% yield) as a white solid. 1H-NMR (400 MHz, CDCl3): δ 8.11 (1H, dd, J=9.4, 2.8 Hz), 7.52 (1H, dd, J=8.6, 5.1 Hz), 7.45-7.36 (3H, m), 7.19-7.14 (1H, m), 7.14-7.09 (2H, m), 7.08-7.03 (2H, m), 7.02-6.93 (3H, m), 6.78-6.72 (1H, m), 6.70-6.64 (1H, m), 6.47 (1H, s), 5.24 (2H, s) ppm.

Workup

  1. stirringThe resulting suspension was stirred for 72 hours at ambient temperature
  2. filtrationThe mixture was then filtered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe crude product was purified by preparative thin-layer chromatography on silica gel eluting with 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-026ec77d6a764d93a5c044621bb36a9b
Source dataset
uspto-grants-2007_09
Patent number
US07265131B2

Reaction notes

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