Triethylamine → HCID 178491245, compound

HRID 1500052Notes

Reaction equation

HRID 1500052 reaction equation
Cl[C:2]1[C:7]([F:8])=[CH:6][NH:5][C:4](=[O:9])[N:3]=1.C(N(CC)CC)C.O.[NH2:18][NH2:19].[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=1>C(O)C>[F:8][C:7]1[C:2]([NH:18]/[N:19]=[CH:26]/[C:25]2[CH:28]=[CH:29][C:22]([O:21][CH3:20])=[CH:23][CH:24]=2)=[N:3][C:4](=[O:9])[NH:5][CH:6]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24654Hydrazine hydrate (1:1)HCID 312444-MethoxybenzaldehydeHCID 178517811HCID 178517811, compound

Product 1

HCID 178491245HCID 178491245, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 25 mL vial was charged with 4-chloro-5-fluoropyrimidin-2(1H)-one (149 mg, 1.00 mmol),* ethanol (4 mL), triethylamine (148 μL, 1.06 mmol), and hydrazine monohydrate (52 μL, 1.07 mmol). The resulting yellow solution was agitated on an orbital shaker at room temperature for 3 h. 4-Methoxybenzaldehyde (123 μL, 1.01 mmol) was added, and the reaction mixture was heated at 50° C. for 16 h. After cooling to room temperature, the crude material was concentrated under reduced pressure and purified by reverse phase flash column chromatography to afford the title compound (49.3 mg, 19%) as a yellow solid: mp 202-208° C.; 1H NMR (300 MHz, DMSO-d6) δ 10.60 (bs, 1H), 10.14 (s, 1H), 8.35 (s, 1H), 7.97 (d, J=8.8 Hz, 2H), 7.38 (t, J=5.9 Hz, 1H), 6.97 (d, J=8.9 Hz, 2H), 3.80 (s, 3H); MS (ESI) ink 263 (M+H)+, 261 (M−H)−. *Driscoll, J. S.; Marquez, V. E.; Plowman, J.; Liu, P. S.; Kelley, J. A.; Barchi, J. J. J. Med. Chem. 1991, 34, 3280-3284. Yamashita, J.; Yamawaki, I; Ueda, S.; Yasumoto, M.; Unemi, N.; Hashimoto, S. Chem. Pharm. Bull. 1982, 30, 4258-4267.

Workup

  1. temperaturethe reaction mixture was heated at 50° C. for 16 h
  2. temperatureAfter cooling to room temperature
  3. concentrationthe crude material was concentrated under reduced pressure
  4. custompurified by reverse phase flash column chromatography

Sources & evidence

ORD record
ord-d986a3687fbd48caacc61c2213c10611
Source dataset
uspto-grants-2015_12
Patent number
US09204653B2

Reaction notes

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