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 2178008노트

반응식

HRID 2178008 반응식
[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]

참가 물질

6

반응물 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 1176UreaHCID 155619131-(1-methyl-1H-pyrazol-4-yl)-2-phenylethanone2회HCID 513483616-(4-aminophenyl)-4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one2회

생성물 1

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

반응 조건

온도
60 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-6cbb30f6f7024776b979471d99d6cbf1
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09067893B2

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