Triethylamine → HCID 178426393, compound

HRID 526512Notes

Reaction equation

HRID 526512 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][N:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][N:16]=3)[C:13]=2[OH:14])=[C:5]([CH3:24])[CH:4]=1)#[N:2].[CH2:25]1[C:28]2([CH2:31][NH:30][CH2:29]2)[CH2:27][O:26]1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>C(#N)C.CN(C=O)C.[OH-].[Na+]>[CH2:25]1[C:28]2([CH2:31][N:30]([C:19]([C:18]3[CH:22]=[CH:23][C:15]([N:12]4[C:13]([OH:14])=[C:9]([C:6]5[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=5[CH3:24])[CH:10]=[N:11]4)=[N:16][CH:17]=3)=[O:20])[CH2:29]2)[CH2:27][O:26]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 231118872-Oxa-6-azaspiro[3.3]heptaneHCID 178426451HCID 178426451, compound

Product 1

HCID 178426393HCID 178426393, compoundYield 10.7%

Reagents, catalysts & solvents 3

HCID 14798Sodium HydroxideCatalystHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×

Procedure

Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (27 mg, 0.084 mmol) and 2-oxa-6-azaspiro[3.3]heptane (12.53 mg, 0.126 mmol) in acetonitrile (1 mL) and DMF (0.5 mL). Then triethylamine (0.035 mL, 0.253 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (19.39 mg, 0.101 mmol) were added and the reaction was stirred at room temperature overnight. A few drops of 1N NaOH solution were added to give a clear solution, and then the mixture was diluted in ACN and purified by HPLC (Waters SunFire C18, 5 μm, ID 30×75 mm, 35-65% ACN/water+0.05% TFA) to give the title compound (3.6 mg, 10.64% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.43 (s, 3H) 4.23-4.30 (m, 2H) 4.53-4.60 (m, 2H) 4.65-4.74 (m, 3H) 7.61-7.88 (m, 4H) 8.24 (br. s., 2H) 8.49-8.78 (m, 2H) 13.27 (br. s., 2H). MS m/z [M+H]+ 402.1.

Workup

  1. customto give a clear solution
  2. custompurified by HPLC (Waters SunFire C18, 5 μm, ID 30×75 mm, 35-65% ACN/water+0.05% TFA)

Sources & evidence

ORD record
ord-4351cddd5f25425db5bb14e7301772c5
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

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