Diisopropylethylamine → HCID 67191863, compound

HRID 551288Notes

Reaction equation

HRID 551288 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][CH:55]=[C: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[CH2:52][CH:53]=[C:54]([C:57]4[CH:58]=[C:59]([CH:62]=[CH:63][CH:64]=4)[C:60]#[N:61])[CH2:55][CH2:56]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 67194524HCID 67194524, compound

Product 1

HCID 67191863HCID 67191863, compoundYield 31.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-phenylethynyl-pyridine-3-carboxylic acid (0.46 g, 2.1 mmol) in anhydrous dimethylformamide (7 ml) is treated with HATU (0.78 g, 2.1 mmol) and diisopropylethylamine (0.98 ml, 5.6 mmol). The reaction mixture is stirred 15 mins. at ambient temperature before being treated with a solution of 3-(1,2,3,6-tetrahydropyridin-4-yl)-benzonitrile (1.9 mmol) in dimethylformamide (6 ml). The reaction mixture is stirred at ambient temperature 3 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 3-[1-(5-phenylethynyl-pyridine-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl]-benzonitrile as a yellow oil (0.23 g). This material is dissolved in methanol (15 ml), cooled to 0° C. and saturated with hydrogen chloride gas. The reaction vessel is sealed and allowed to stand at 0° C. for 18 hours. The reaction mixture is concentrated to dryness under vacuum, redissolved in methanol (15 ml) and cooled to 0° C. The solution is saturated with ammonia gas and the vessel sealed before being allowed to stand at 0° C. for 48 hours. The reaction mixture is concentrated to dryness under vacuum and the residue chromatographed on silica gel (dichloromethane/methanol 9:1) to give the title compound as a yellow amorphous solid (0.2 g). 1H NMR (DMSO, 500 MHz) δ8.85 (s, 1H), 8.67 (s, 1H), 8.10 (s, 1H), 7.85 (s, 1H), 7.80 (m, 1H), 7.75 (m, 1H), 7.60 (m, 3H), 7.48 (m, 3H), 6.38 (m, 1H), 4.38 (br m, 1H), 4.19 (br m, 1H), 3.90 (br m, 1H), 3.60 (br m, 1H), 2.63 (br m, 2H). EI MS M++H: 407.

Workup

  1. stirringThe reaction mixture is stirred at ambient temperature 3 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-4a6b62e9a0704b19a1b02bbd86f7166a
Source dataset
uspto-grants-2011_05
Patent number
US07947684B2

Reaction notes

Loading…