Methyl 2-aminopyridine-4-carboxylate → 3-methyl-2-[2-(4-cyanophenyl)ethyl]imidazo[1,2-a]pyridin-7-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)amide

HRID 2288520Notes

Reaction equation

HRID 2288520 reaction equation
[CH3:1][C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11](O)=[O:12])=[CH:10][C:5]2=[N:4][C:3]=1[CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=1.BrC(C)C(=O)C=CC1C=CC(C#N)=CC=1.NC1C=C(C(OC)=O)C=CN=1.[CH2:50]([O:52][C:53]([CH2:55][CH2:56][NH:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)=[O:54])[CH3:51].C(OCC)(=O)C.C(O)C.N>S(Cl)(Cl)=O>[C:58]1([N:57]([CH2:56][CH2:55][C:53]([O:52][CH2:50][CH3:51])=[O:54])[C:11]([C:9]2[CH:8]=[CH:7][N:6]3[C:2]([CH3:1])=[C:3]([CH2:14][CH2:15][C:16]4[CH:17]=[CH:18][C:19]([C:22]#[N:23])=[CH:20][CH:21]=4)[N:4]=[C:5]3[CH:10]=2)=[O:12])[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=1

Participants

7

Reactant 5

HCID 236984Methyl 2-aminopyridine-4-carboxylateHCID 10910393beta-Alanine, N-phenyl-, ethyl esterHCID 184123193-Methyl-2-[2-(4-cyanophenyl)ethyl]imidazo[1,2-a]pyridin-7-yl-carboxylic acidHCID 542928874-Bromo-1-(4-cyanophenyl)-1-penten-3-oneHCID 86587043Ethyl acetate ethanol ammonia

Product 1

HCID 184123873-methyl-2-[2-(4-cyanophenyl)ethyl]imidazo[1,2-a]pyridin-7-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)amide

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

1.4 g (4.6 mmol) of 3-methyl-2-[2-(4-cyanophenyl)ethyl]-imidazo[1.2-a]pyridin-7-yl-carboxylic acid (prepared from 4-bromo-1-(4-cyanophenyl)-1-penten-3-one and methyl 2-aminopyridine-4-carboxylate analogously to Y. Katsura et al. Chem. Pharm. Bull. 1992, 40, 1424-1438) were suspended in 15 ml of thionyl chloride and heated to boiling for 1 hour until fully dissolved. After the thionyl chloride had been distilled off the acid chloride was dissolved in 15 ml of pyridine without any further purification and at 0° C. mixed with 1.0 g (5.2 mmol) of N-(2-ethoxycarbonylethyl)-aniline. After 1 hour the solvent was distilled off, the residue was taken up in 30 ml of methylene chloride, washed with 15 ml of 1N hydrochloric acid and dried with sodium sulphate. After distillation of the solvent and chromatography (silica gel; methylene chloride/ethanol=0 to 2%) a brown oil was obtained. Yield: 1.48 g (64% of theory), Rf value: 0.73 (silica gel; ethyl acetate/ethanol/ammonia=90:10:1)

Workup

  1. temperatureheated
  2. dissolutionuntil fully dissolved
  3. distillationAfter the thionyl chloride had been distilled off the acid chloride
  4. dissolutionwas dissolved in 15 ml of pyridine without any further purification and at 0° C.
  5. distillationAfter 1 hour the solvent was distilled off
  6. washwashed with 15 ml of 1N hydrochloric acid
  7. dry with materialdried with sodium sulphate
  8. distillationAfter distillation of the solvent and chromatography (silica gel; methylene chloride/ethanol=0 to 2%) a brown oil
  9. customwas obtained

Sources & evidence

ORD record
ord-d2625d362df14aad8a73fe2d95adcba6
Source dataset
uspto-grants-2000_07
Patent number
US06087380

Reaction notes

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