Hydrochloric Acid → 2-hydroxy-4-(6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-5-phenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acid

HRID 924913Notes

Reaction equation

HRID 924913 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7](=O)[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:4]=[N:3]1.NC1C=CC(C2[NH:28][C:27](=[O:29])[NH:26][CH:25]([C:30]3[CH:35]=[C:34]([N+]([O-])=O)[C:33](O)=[C:32]([O:40]CC)[CH:31]=3)C=2C2C=CC=CC=2)=CC=1.N[C:50](N)=[O:51].Cl.CC[OH:56]>>[OH:40][C:32]1[CH:31]=[C:30]([CH:25]2[C:8]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:7]([C:5]3[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=3)[NH:28][C:27](=[O:29])[NH:26]2)[CH:35]=[CH:34][C:33]=1[C:50]([OH:51])=[O:56]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 1176UreaHCID 155619131-(1-methyl-1H-pyrazol-4-yl)-2-phenylethanone2×HCID 513483616-(4-aminophenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one2×

Product 1

HCID 668257572-hydroxy-4-(6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-5-phenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acidYield 20%

Conditions

Temperature
60 °C

Procedure

A mixture of 1-(1-methyl-1H-pyrazol-4-yl)-2-phenylethanone (Intermediate 88) (150 mg, 0.75 mmol), methyl 4-formyl-2-hydroxybenzoate (Intermediate 84) (135 mg, 0.75 mmol), urea (138 mg, 2.3 mmol) and conc. HCl (0.5 mL) in EtOH (5 mL) was refluxed under N2 atmosphere overnight. The mixture was concentrated under reduced pressure. The residue was taken up in MeOH (10 mL) and aq. NaOH (2 M, 10 mL) and was stirred at 60° C. under N2 overnight. The mixture was cooled, and then acidified with aqueous HCl (2 M, 12 mL) to pH=3 followed by a standard aqueous/EtOAc workup and purification by prep-HPLC (0.1% TFA as additive) to give Compound 167 (58 mg, 2-step yield 20%) as off-white solid. 1H NMR (CD3OD 400 MHz): δ 7.81 (d, J=8.0 Hz, 1H), 7.38 (s, 1H), 7.25-7.20 (m, 3H), 6.88-6.78 (m, 3H), 6.84 (d, J=8.0 Hz, 1H), 6.82 (s, 1H), 5.17 (s, 1H), 3.77 (s, 3H). MS (ESI): m/z 390.7 [M+1]+.

Workup

  1. temperaturewas refluxed under N2 atmosphere overnight
  2. concentrationThe mixture was concentrated under reduced pressure
  3. temperatureThe mixture was cooled
  4. customEtOAc workup and purification by prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record
ord-9410d81efe17452cbeedd39d1698895a
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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