Triethylamine → HCID 66685416, compound

HRID 1500608Notes

Reaction equation

HRID 1500608 reaction equation
O([C:8]([NH:10][C:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][C:12]=1[C:24]([O:26]CC)=O)=[O:9])C1C=CC=CC=1.C(N(CC)CC)C.Cl.[NH2:37][N:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1>C1COCC1>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][C:11]2[NH:10][C:8](=[O:9])[N:37]([N:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)[C:24](=[O:26])[C:12]=2[CH2:13]1)=[O:18])([CH3:21])([CH3:22])[CH3:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 3017392Pyrrolidin-1-amine monohydrochlorideHCID 66685805Ethyl-4-phenoxycarbonylamino-1-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Product 1

HCID 66685416HCID 66685416, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
68 °C

Procedure

Under nitrogen, 1-tert-butyl 3-ethyl 4-(phenoxycarbonylamino)-5,6-dihydropyridine-1,3(2H)-dicarboxylate (6.14 g) was dissolved in THF (50 ml) and 1-aminopyrrolidine hydrochloride (2.31 g), triethylamine (6.58 ml) and 1,8-diazabicyclo[5.4.0]und-7-ene (0.24 ml) were added, and the resultant mixture was stirred at room temperature for 2 hours. Thereafter, the reaction solution was stirred at 50° C. for 2 hours and 68° C. for 3 hours. After consumption of the raw materials was confirmed by TLC or LC/MS, to the reaction mixture 2 N sodium hydroxide solution (15.7 ml) was added at 0° C., and the resultant mixture was stirred at room temperature for two days. Thereafter, the solution was stirred at 50° C. for 3 hours and further 2 N sodium hydroxide solution (10 ml) was added at the same temperature. The reaction mixture was stirred at 68° C. for 2 hours. After the completion of the reaction was confirmed by TLC or LC/MS, the solution was cooled to room temperature, 2 N hydrochloric acid (30 ml) and a saturated ammonium chloride solution were added, the resultant mixture was extracted with ethyl acetate and dried over sodium sulfate. The solution was filtrated, concentrated and purified by silica gel chromatography to obtain desired tert-butyl-2,4-dioxo-3-(pyrrolidin-1-yl)-1,2,3,4,7,8-hexahydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate in an amount of 3.19 g (yield 60%).

Workup

  1. customAfter consumption of the raw materials
  2. additionwas added at 0° C.
  3. stirringthe resultant mixture was stirred at room temperature for two days
  4. stirringThereafter, the solution was stirred at 50° C. for 3 hours
  5. additionfurther 2 N sodium hydroxide solution (10 ml) was added at the same temperature
  6. stirringThe reaction mixture was stirred at 68° C. for 2 hours
  7. temperaturethe solution was cooled to room temperature
  8. addition2 N hydrochloric acid (30 ml) and a saturated ammonium chloride solution were added
  9. extractionthe resultant mixture was extracted with ethyl acetate
  10. dry with materialdried over sodium sulfate
  11. filtrationThe solution was filtrated
  12. concentrationconcentrated
  13. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-00352b47c13c4408bb87fb7c37edc818
Source dataset
uspto-grants-2015_12
Patent number
US09206173B2

Reaction notes

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