Hydrochloric Acid → 4-(4-(2H-tetrazol-5-yl)phenyl)-6-(pyridin-3-yl)-5-(thiophen-3-yl)-3,4-dihydropyrimidin-2(1H)-one

HRID 2178007Notes

Reaction equation

HRID 2178007 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=O)[CH2:8][C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)[CH:2]=1.[N:15]1[NH:16][N:17]=[N:18][C:19]=1[C:20]1[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=1.[NH2:28][C:29]([NH2:31])=[O:30].Cl>CCO>[N:15]1[NH:16][N:17]=[N:18][C:19]=1[C:20]1[CH:27]=[CH:26][C:23]([CH:24]2[C:8]([C:9]3[CH:13]=[CH:12][S:11][CH:10]=3)=[C:7]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[NH:31][C:29](=[O:30])[NH:28]2)=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 27606064-(1H-1,2,3,4-tetrazol-5-yl)benzaldehydeHCID 610560411-(Pyridin-3-yl)-2-(thiophen-3-yl)ethanone2×

Product 1

HCID 668259114-(4-(2H-tetrazol-5-yl)phenyl)-6-(pyridin-3-yl)-5-(thiophen-3-yl)-3,4-dihydropyrimidin-2(1H)-oneYield 35.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-(pyridin-3-yl)-2-(thiophen-3-yl)ethanone (Intermediate 56) (80 mg, 0.39 mmol), 4-(2H-tetrazol-5-yl)benzaldehyde (300 mg), urea (120 mg, 2.0 mmol) and conc. HCl (0.5 mL) in EtOH (5 mL) was refluxed under N2 overnight. The mixture was concentrated under reduced pressure and purified by prep-HPLC (0.1% TFA as additive) to give Compound 166 (56 mg, yield 35%) as yellow solid. 1H NMR (CD3OD 400 MHz): δ 8.71-8.61 (m, 2H), 8.30 (d, J=8.0 Hz, 1H), 8.04 (d, J=8.0 Hz, 2H), 7.85-7.78 (m, 1H), 7.65 (d, J=8.0 Hz, 2H), 7.22 (dd, J=2.8 Hz, J=4.8 Hz, 1H), 6.89 (dd, J=1.6 Hz, J=3.2 Hz, 1H), 6.56 (dd, J=1.2 Hz, J=5.2 Hz, 1H), 5.50 (s, 1H). MS (ESI): m/z 402.3 [M+1]+.

Workup

  1. temperaturewas refluxed under N2 overnight
  2. concentrationThe mixture was concentrated under reduced pressure
  3. custompurified by prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record
ord-3d440ea7177c44f08441532c6d51c8ed
Source dataset
uspto-grants-2015_06
Patent number
US09067893B2

Reaction notes

Loading…