4-Fluorobenzylamine → 2-PYRIMIDINECARBOXAMIDE

HRID 2219056Notes

Reaction equation

HRID 2219056 reaction equation
S(O)(=O)(=[O:3])C.[N:6]1[CH:11]=[CH:10][CH:9]=[N:8][CH:7]=1.FC1C=CC([CH2:17][NH2:18])=CC=1>CCO>[N:6]1[CH:11]=[CH:10][CH:9]=[N:8][C:7]=1[C:17]([NH2:18])=[O:3]

Participants

4

Reactant 2

HCID 673264-FluorobenzylamineHCID 19894525HCID 19894525, compound

Product 1

HCID 151497992-PYRIMIDINECARBOXAMIDEYield 126.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of seven-membered ring-pyrimidine mesylate 2 (6 g) in EtOH (80 mL) was added 4-fluorobenzylamine (5.060 g). The resulting solution was reflux for 8 h. (100% conversion by HPLC). The reaction mixture was concentrated to about 20 mL total volume, and 80 mL of EtOAc was added. To the resulting solution was added 20% brine (15 mL), 4 N HCl (15 mL), and water 10 mL). After a phase cut, the aqueous layer was back-extracted with EtOAc (25 mL). The combined organic layers were washed with 4 N HCl: 20% brine (1:1, 3×15 mL), brine (15 mL). The organic solution was concentrated to a total volume about 30 mL. Hexane (70 mL) was slowly added to the solution over 1 h. The resulting slurry was aged at 0-5° C. for 1 h. The crystalline solid was filtered off, washed with hexane:EtOAc (4:1, 50 mL), dried under vacuum with nitrogen sweep to afford seven-membered ring-pyrimidine amide 10 (5.30 g, 86%, HPLC>97A %). 1H NMR (CDCl3, 400 MHz) δ: 11.85 (br s, 1H), 7.84 (br s, 0.5H), 7.68 (br s, 0.5H), 7.31 (m, 2H), 7.04 (m, 2H), 5.40-4.90 (m, 2H), 4.53 (m, 2H), 3.38 (m, 1H), 2.87 (s, 3H), 2.20-2.15 (m, 3H), 1.90-1.40 (m, 3H), 1.37 (s, 9H).

Workup

  1. temperatureThe resulting solution was reflux for 8 h. (100% conversion by HPLC)
  2. concentrationThe reaction mixture was concentrated to about 20 mL total volume, and 80 mL of EtOAc
  3. additionwas added
  4. additionTo the resulting solution was added 20% brine (15 mL), 4 N HCl (15 mL), and water 10 mL)
  5. extractionAfter a phase cut, the aqueous layer was back-extracted with EtOAc (25 mL)
  6. washThe combined organic layers were washed with 4 N HCl
  7. concentrationThe organic solution was concentrated to a total volume about 30 mL
  8. additionHexane (70 mL) was slowly added to the solution over 1 h
  9. filtrationThe crystalline solid was filtered off
  10. washwashed with hexane:EtOAc (4:1, 50 mL)
  11. customdried under vacuum with nitrogen sweep

Sources & evidence

ORD record
ord-a5cd751ce63443ab9e2bb725b7a0a7e1
Source dataset
uspto-grants-2008_08
Patent number
US07414045B2

Reaction notes

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