Hydrochloric Acid → 6-(Tert-butoxycarbonyl)-3-dimethylamino-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-2,4-dione

HRID 1500606Notes

Reaction equation

HRID 1500606 reaction equation
C(O[C:4]([C:6]1[CH2:7][N:8]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:9][CH2:10][C:11]=1[NH:12][C:13]([O:15]C1C=CC=CC=1)=O)=[O:5])C.C[NH:30][NH:31][CH3:32].[CH2:33]1CCN2C(=NCCC2)CC1.NC(N)=O.[OH-].[Na+].Cl>C1COCC1>[C:25]([O:24][C:22]([N:8]1[CH2:9][CH2:10][C:11]2[NH:12][C:13](=[O:15])[N:30]([N:31]([CH3:32])[CH3:33])[C:4](=[O:5])[C:6]=2[CH2:7]1)=[O:23])([CH3:26])([CH3:27])[CH3:28]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 1176UreaHCID 13221,2-Dimethylhydrazine2×HCID 14798Sodium HydroxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 66685805Ethyl-4-phenoxycarbonylamino-1-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-3-carboxylate

Product 1

HCID 666854156-(Tert-butoxycarbonyl)-3-dimethylamino-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-2,4-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl-4-phenoxycarbonylamino-1-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-3-carboxylate (5.0 g) was dissolved in THF (50 ml) and dimethyl hydrazine (1.46 ml) and DBU (0.2 ml) were added and the resultant mixture was stirred at room temperature for 2 hours. Dimethylhydrazine (0.73 ml) and DBU (0.2 ml) were added and the resultant mixture was further stirred at room temperature for 2 hours. After production of an intermediate (urea) was confirmed by TLC, a 5 N aqueous sodium hydroxide solution (5 ml) was added and the resultant mixture was further stirred at room temperature overnight. To the reaction solution, 6 N hydrochloric acid was added to neutralize and the resultant mixture was then concentrated. To the residue, water was added and the mixture was extracted with ethyl acetate. After the organic layer was washed with a saturated saline solution, the organic layer was dried over sodium sulfate, filtrated and concentrated. The resultant residue was purified by medium-pressure silica gel column chromatography (solvent; ethyl acetate:hexane=50:50 to 100:0). To the resultant amorphous substance, diethyl ether was added to obtain a precipitate by filtration. The titled compound (3.34 g) was obtained as a white powder.

Workup

  1. concentrationthe resultant mixture was then concentrated
  2. additionTo the residue, water was added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washAfter the organic layer was washed with a saturated saline solution
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. filtrationfiltrated
  7. concentrationconcentrated
  8. customThe resultant residue was purified by medium-pressure silica gel column chromatography (solvent; ethyl acetate:hexane=50:50 to 100:0)
  9. additionTo the resultant amorphous substance, diethyl ether was added
  10. customto obtain a precipitate
  11. filtrationby filtration

Sources & evidence

ORD record
ord-bda22d87747f498d98b2bfbe1caa3f4d
Source dataset
uspto-grants-2015_12
Patent number
US09206173B2

Reaction notes

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