Hydrochloric Acid → 3-Ethoxy-2-hydroxy-5-(2-oxo-6-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acid

HRID 924881Notes

Reaction equation

HRID 924881 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.[CH2:15]([O:17][C:18]1[C:19]([OH:29])=[C:20]([CH:24]=[C:25]([CH:27]=O)[CH:26]=1)[C:21]([OH:23])=[O:22])[CH3:16].[NH2:30][C:31]([NH2:33])=[O:32].Cl>CCO>[CH2:15]([O:17][C:18]1[C:19]([OH:29])=[C:20]([CH:24]=[C:25]([CH:27]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:33][C:31](=[O:32])[NH:30]2)[CH:26]=1)[C:21]([OH:23])=[O:22])[CH3:16]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 212616363-Ethoxy-5-formyl-2-hydroxybenzoic acid2×HCID 610560411-(Pyridin-3-yl)-2-(thiophen-3-yl)ethanone2×

Product 1

HCID 668246513-Ethoxy-2-hydroxy-5-(2-oxo-6-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acidYield 33%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-(pyridin-3-yl)-2-(thiophen-3-yl)ethanone (Intermediate 56) (372 mg, 1.83 mmol), 3-ethoxy-5-formyl-2-hydroxybenzoic acid (Intermediate 62) (350 mg, 1.67 mmol), urea (300 mg, 5.00 mmol) and HCl (12 M, 0.14 mL, 1.67 mmol) in EtOH (10 mL) was refluxed overnight. The mixture was concentrated in vacuo and purified by preparative HPLC to give Compound 126 (240 mg, yield 33%) as a yellow solid. 1H NMR (DMSO-d6 400 MHz): δ 11.35 (br, 1H), 8.87 (d, J=1.6 Hz, 1H), 8.56 (dd, J=1.6 Hz, J=5.2 Hz, 1H), 8.45 (d, J=1.6 Hz, 1H), 7.80 (d, J=8.0 Hz, 1H), 7.56 (s, 1H), 7.51-7.48 (m, 1H), 7.42 (d, J=2.0 Hz, 1H), 7.24-7.22 (m, 1H), 7.15 (d, J=2.0 Hz, 1H), 6.87 (dd, J=1.2 Hz, J=3.2 Hz, 1H), 6.33 (dd, J=1.2 Hz, J=4.8 Hz, 1H), 5.16 (d, J=2.4 Hz, 1H), 4.03-3.95 (m, 2H), 1.31 (t, J=6.8 Hz, 3H); MS (ESI): m/z 438.0 [M+1]+;

Workup

  1. temperaturewas refluxed overnight
  2. concentrationThe mixture was concentrated in vacuo
  3. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-ec2143e5c8bb4e1993aa9d6625ce11ff
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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