Tetrahydrofuran → HCID 15950716, compound

HRID 1619208Notes

Reaction equation

HRID 1619208 reaction equation
CON(C)[C:4]([C:6]1[CH2:7][CH2:8][N:9]([C:12]2[N:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH2:10][CH:11]=1)=[O:5].[CH2:19]1[CH2:23]O[CH2:21][CH2:20]1>>[C:19]1([C:23]2[CH:8]=[CH:7][CH:6]=[CH:11][CH:10]=2)[CH:16]=[CH:15][C:14]([C:4]([C:6]2[CH2:7][CH2:8][N:9]([C:12]3[N:13]=[CH:14][CH:15]=[CH:16][N:17]=3)[CH2:10][CH:11]=2)=[O:5])=[CH:21][CH:20]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 86609049HCID 86609049, compound

Product 1

HCID 15950716HCID 15950716, compoundYield 30%

Procedure

To a solution of 1-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridin-4-carboxylic acid methoxy-methyl amide (48 mg, 0.196 mmol) in THF (1 ml), was added 1-biphenyl-4-yl magnesium bromide (0.5 M in THF) at 0° C. The mixture was stirred at this temperature for 1 hour and quenched with addition of water (5 ml) and EtOAc (20 ml). The aqueous phase was further extracted with EtOAc (2×8 ml). The combined organic layers were washed with brine (5 ml), dried (MgSO4), filtered, and concentrated under reduced pressure to furnish the crude product. This material was purified by column chromatography (4% MeOH/CH2Cl2) to give the title compound (20 mg, 30%) as an off-white solid: 1H NMR (CDCl3, 400 MHz) δ 8.38 (d, J=6.4 Hz, 2H), 7.82-7.42 (m, 9H), 6.70 (m, 1H), 6.58 (t, J=6.4 Hz, 1H), 4.51 (m, 2H), 4.13 (t, J=5.6 Hz, 2H), 2.72 (m, 2H); MS calc'd for C22H20N3O [M+H]+: 342; Found: 342.

Workup

  1. customquenched with addition of water (5 ml) and EtOAc (20 ml)
  2. extractionThe aqueous phase was further extracted with EtOAc (2×8 ml)
  3. washThe combined organic layers were washed with brine (5 ml)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto furnish the crude product
  8. customThis material was purified by column chromatography (4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ddbd288a8212413384f020bfb9e70626
Source dataset
uspto-grants-2014_07
Patent number
US08772291B2

Reaction notes

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