Diethylamine → HCID 53325186, compound

HRID 1663181Notes

Reaction equation

HRID 1663181 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:6][CH2:5]2.[F:12][C:13]1[CH:14]=[C:15]([C:19]#[CH:20])[CH:16]=[CH:17][CH:18]=1.C(NCC)C>CN(C=O)C.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.[Cu]I>[F:12][C:13]1[CH:14]=[C:15]([C:19]#[C:20][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[C:7](=[O:11])[NH:6][CH2:5]3)[CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 3

HCID 8021DiethylamineHCID 5202181-Ethynyl-3-fluorobenzeneHCID 226071195-bromo-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 53325186HCID 53325186, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
60 °C

Procedure

To a solution of 5-bromoisoindolin-1-one III-3 (100 mg, 0.47 mmol) in DMF (2 mL) was added 3-fluorophenylacetylene III-4 (67 mg, 0.56 mmol), Pd(Ph3P)4 (27 mg, 0.02 mmol), CuI (9 mg, 0.04 mmol) and diethylamine (200 μL). The reaction vessel was sealed and heated at 60° C. for 1 h in a microwave reactor. The reaction was cooled to rt, diluted with EtOAc:hexanes (2:1, 8 mL) and washed with water (2×5 mL) and brine (5 mL). The organic phase was dried over MgSO4, filtered and concentrated under vacuum. The crude product was purified by mass directed preparative HPLC to afford 5-((3-fluorophenyl)ethynyl)isoindolin-1-one III-5 (42 mg, 35%) as a light brown solid; 1H-nmr (400 MHz, CDCl3) δ 7.92 (d, J=8.0 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.56 (s, 1H), 7.40-7.31 (m, 2H), 7.28-7.22 (m, 1H), 7.14-7.07 (m, 1H), 5.36 (s, 2H); LC (214 nM) 3.38 min (>98%); MS (ESI) m/z=253.1.

Workup

  1. customThe reaction vessel was sealed
  2. temperatureThe reaction was cooled to rt
  3. washwashed with water (2×5 mL) and brine (5 mL)
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude product was purified by mass

Sources & evidence

ORD record
ord-a29c52ea76704bd482006fdf81b4f653
Source dataset
uspto-grants-2011_10
Patent number
US08034806B2

Reaction notes

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