Diisopropylethylamine → 3-[1-(5-Phenylethynyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzonitrile

HRID 551287Notes

Reaction equation

HRID 551287 reaction equation
[C:1]1([C:7]#[C:8][C:9]2[CH:10]=[C:11]([C:15]([OH:17])=O)[CH:12]=[N:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH:51]1[CH2:56][CH2:55][CH:54]([C:57]2[CH:58]=[C:59]([CH:62]=[CH:63][CH:64]=2)[C:60]#[N:61])[CH2:53][CH2:52]1>CN(C)C=O>[C:1]1([C:7]#[C:8][C:9]2[CH:10]=[C:11]([C:15]([N:51]3[CH2:56][CH2:55][CH:54]([C:57]4[CH:58]=[C:59]([CH:62]=[CH:63][CH:64]=4)[C:60]#[N:61])[CH2:53][CH2:52]3)=[O:17])[CH:12]=[N:13][CH:14]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27792365-(2-Phenyleth-1-Ynyl)Nicotinic AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 214481663-(Piperidin-4-yl)benzonitrile

Product 1

HCID 671944903-[1-(5-Phenylethynyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzonitrileYield 45.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-phenylethynyl-pyridine-3-carboxylic acid (0.75 g, 3.3 mmol) in anhydrous dimethylformamide (9 ml) is treated with HATU (1.27 g, 3.3 mmol) and diisopropylethylamine (1.1 ml, 6.1 mmol). The reaction mixture is stirred 15 mins. at ambient temperature before being treated with a solution of 3-(piperidin-4-yl)-benzonitrile (0.6 g, 3 mmol) in dimethylformamide (6 ml). The reaction mixture is stirred at ambient temperature 2 hours, concentrated under vacuum and the residue partitioned between ethyl acetate (200 ml) and saturated aqueous sodium bicarbonate ((45 ml). The organic layer is dried (magnesium sulfate), concentrated under vacuum and the residue chromatographed on silica gel (dichloromethane/methanol 39:1) to give the title compound as a yellow oil (0.53 g). 1H NMR (CDCl3, 500 MHz) δ8.80 (s, 1H), 8.63 (s, 1H), 8.00 (s, 1H), 7.50 (m, 9H), 4.90 (br m, 1H), 3.85 (br m, 1H), 3.28 (m, 1H), 2.90 (m, 2H), 1.91 (m, 1H), 1.75 (m, 3H). EI MS M++H: 392.

Workup

  1. stirringThe reaction mixture is stirred at ambient temperature 2 hours
  2. concentrationconcentrated under vacuum
  3. customthe residue partitioned between ethyl acetate (200 ml) and saturated aqueous sodium bicarbonate ((45 ml)
  4. dry with materialThe organic layer is dried (magnesium sulfate)
  5. concentrationconcentrated under vacuum
  6. customthe residue chromatographed on silica gel (dichloromethane/methanol 39:1)

Sources & evidence

ORD record
ord-5371d52629a540afa08e1bf67f9bebc0
Source dataset
uspto-grants-2011_05
Patent number
US07947684B2

Reaction notes

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