Diisopropylethylamine → HCID 22051047, compound

HRID 1832026Notes

Reaction equation

HRID 1832026 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([CH3:13])[N:10]([CH2:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[C:9](=[O:21])[C:8]=1[Br:22])(=O)=O.CCN(C(C)C)C(C)C.[F:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]#[CH:42])=[CH:37][CH:36]=1>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:22][C:8]1[C:9](=[O:21])[N:10]([CH2:14][C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[C:11]([CH3:13])=[CH:12][C:7]=1[CH2:42][CH2:41][C:38]1[CH:39]=[CH:40][C:35]([F:34])=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5226271-Ethynyl-4-fluorobenzeneHCID 21035326HCID 21035326, compound

Product 1

HCID 22051047HCID 22051047, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of 3-bromo-6-methyl-2-oxo-1-(pyridin-3-ylmethyl)-1,2-dihydropyridin-4-yl trifluoromethanesulfonate (0.6675 g, 1.56 mmol) in DMF (9 mL), DIEA (0.35 mL, 2.03 mmol), 4-fluorophenylacetylene (0.235 mL, 1.95 mmol) and PdCl2(PPh3)2 (0.11 g) were added. The reaction mixture stirred at room temperature under nitrogen for 1 hour and then heated in an oil bath (65° C.) under nitrogen overnight. The solvents were distilled in vacuo and the residue was purified by flash column chromatography (5% methanol in ethyl acetate). The extracts were concentrated to afford the desired compound (0.432 g, 69%) after drying. 1H-NMR (CD3OD, 400 MHz) δ 8.45 (s, 2H), 7.96 (s, 1H), 7.64 (m, 3H), 7.41 (dd, 1H, J=4.8 Hz, 4.8 Hz), 7.18 (t, 2H, J=8.8 Hz), 6.46 (s, 1H), 5.45 (s, 2H), 2.37 (s, 3H); ES-HRMS m/z 397.0361/399.0310 (M+H calculated for C20H15N2OFBr requires 397.0346/399.0328). Step 3. Preparation of 3-bromo-4-[2-(4-fluorophenyl)ethyl]-6-methyl-1-(pyridin-3-ylmethyl)pyridin-2(1H)-one

Workup

  1. temperatureheated in an oil bath (65° C.) under nitrogen overnight
  2. distillationThe solvents were distilled in vacuo
  3. customthe residue was purified by flash column chromatography (5% methanol in ethyl acetate)
  4. concentrationThe extracts were concentrated

Sources & evidence

ORD record
ord-29ff2f93d891458fa25df1b5dcf89660
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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