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

HRID 1500607Notes

Reaction equation

HRID 1500607 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.C1CCN2C(=[N:33]CCC2)CC1.N[C:41](N)=[O:42].[OH-].[Na+].Cl>C1COCC1.Cl.CON.C(N(CC)CC)C>[C:25]([O:24][C:22]([N:8]1[CH2:9][CH2:10][C:11]2[NH:12][C:13](=[O:15])[N:33]([O:42][CH3:41])[C:4](=[O:5])[C:6]=2[CH2:7]1)=[O:23])([CH3:26])([CH3:27])[CH3:28]

Participants

9

Reactant 5

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

Product 1

HCID 666858106-(Tert-butoxycarbonyl)-3-methoxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-2,4-dione

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×HCID 521874O-Methylhydroxylamine hydrochlorideSolvent2×

Procedure

Ethyl-4-phenoxycarbonylamino-1-tert-butoxycarbonyl-1,2,5,6-tetrahydropyridine-3-carboxylate (3.0 g) was dissolved in THF (30 ml) and O-methylhydroxylamine hydrochloride (3.2 g), triethylamine (5.35 ml) and DBU (0.3 ml) were added to the solvent, and the resultant mixture was stirred at room temperature overnight. O-methylhydroxylamine hydrochloride (3.2 g) and triethylamine (5.35 ml) were added and the resultant mixture was further stirred at room temperature for 6 hours. After production of an intermediate (urea) was confirmed by TLC, a 5 N 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, and the resultant mixture was neutralized and concentrated to obtain a precipitate by filtration. The resultant crude crystal was dissolved in methylene chloride-methanol and ethyl acetate was added to obtain a precipitate by filtration. The resultant crude crystal was purified by medium-pressure silica gel column chromatography (solvent; methanol:ethyl acetate=0:100 to 10:90). The titled compound (2.21 g) was obtained as a white powder.

Workup

  1. concentrationconcentrated
  2. customto obtain a precipitate
  3. filtrationby filtration
  4. dissolutionThe resultant crude crystal was dissolved in methylene chloride-methanol
  5. additionethyl acetate was added
  6. customto obtain a precipitate
  7. filtrationby filtration
  8. customThe resultant crude crystal was purified by medium-pressure silica gel column chromatography (solvent; methanol:ethyl acetate=0:100 to 10:90)

Sources & evidence

ORD record
ord-b60d0c76baca48018e4ccd016090dbd2
Source dataset
uspto-grants-2015_12
Patent number
US09206173B2

Reaction notes

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