Diisopropylethylamine → HCID 69030986, compound

HRID 489591

Reaction equation

HRID 489591 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.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[C:51]([O:55][C:56]([N:58]([CH2:66][C:67]1[CH:68]=[C:69]([CH:73]2[CH2:78][CH2:77][NH:76][CH2:75][CH2:74]2)[CH:70]=[CH:71][CH:72]=1)[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[O:57])([CH3:54])([CH3:53])[CH3:52]>CN(C)C=O>[C:62]([O:61][C:59]([N:58]([CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[C:69]([CH:73]2[CH2:74][CH2:75][N:76]([C:15]([C:11]3[CH:12]=[N:13][CH:14]=[C:9]([C:8]#[C:7][C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH:10]=3)=[O:17])[CH2:77][CH2:78]2)[CH:68]=1)[C:56]([O:55][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:57])=[O:60])([CH3:63])([CH3:64])[CH3:65]

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 22266157HCID 22266157, compound

Product 1

HCID 69030986HCID 69030986, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-phenylethynyl-pyridine-3-carboxylic acid (0.25 g, 1.1 mmol) in anhydrous dimethylformamide (5 ml) was treated with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.42 g, 1.1 mmol) and diisopropylethylamine (0.5 ml, 3 mmol). This mixture was stirred 15 minutes at ambient temperature and then treated with a solution of 4-{3-[N,N-Bis-(tert-butoxycarbonyl)aminomethyl]-phenyl}-piperidine (0.39 g, 1.0 mmol) in dimethylformamide (5 ml). After stirring at ambient temperature for 18 hours the reaction mixture was concentrated under vacuum. The residue was partitioned between ethyl acetate (50 ml) and saturated aqueous sodium bicarbonate (15 ml). The organic layer was dried over magnesium sulfate and then concentrated under vacuum. The residue was subjected to chromatography on silica gel eluting with a mixture of dichloromethane and methanol (49:1, v/v) to give N,N-bis-(tert-butoxycarbonyl)-3-[1-(5-phenylethynyl -pyridine-3-carbonyl)-piperidin-4-yl]-benzylamine as a yellow oil (0.25 g). 1H NMR [(CD3)2SO, 500 MHz]: δ 8.82 (s, 1H), 8.62 (s, 1H), 8.02 (s, 1H), 7.61 (m, 2H), 7.45 (m, 3H), 7.30 (m, 1H), 7.20 (m, 1H), 7.15 (m, 1H), 7.04 (m, 1H), 4.68 (s, 2H), 4.62 (br m, 1H), 3.60 (br m, 1H), 3.23 (br m, 1H), 2.85 (m, 2H), 1.83 (br m, 1H), 1.65 (m, 3H), 1.39 (s, 18H). MS(EI): 596(M++H).

Workup

  1. stirringAfter stirring at ambient temperature for 18 hours the reaction mixture
  2. concentrationwas concentrated under vacuum
  3. customThe residue was partitioned between ethyl acetate (50 ml) and saturated aqueous sodium bicarbonate (15 ml)
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. concentrationconcentrated under vacuum
  6. additionThe residue was subjected to chromatography on silica gel eluting with a mixture of dichloromethane and methanol (49:1

Sources & evidence

ORD record
ord-249999b5947348be805c0844d106fbed
Source dataset
uspto-grants-2005_12
Patent number
US06977263B2

Linked notes

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