Ammonia → 6-methoxy-5-(N-methylpiperidin-4-yloxy)-3,4-dihydroquinazolin-4-one

HRID 1826284Notes

Reaction equation

HRID 1826284 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[OH:17][C:18]1[C:27]([O:28][CH3:29])=[CH:26][CH:25]=[C:24]2[C:19]=1[C:20](=[O:38])[N:21](COC(=O)C(C)(C)C)[CH:22]=[N:23]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH:59]1[CH2:64][CH2:63][N:62]([CH3:65])[CH2:61][CH2:60]1.N>C(Cl)Cl>[CH3:29][O:28][C:27]1[C:18]([O:17][CH:59]2[CH2:64][CH2:63][N:62]([CH3:65])[CH2:61][CH2:60]2)=[C:19]2[C:24](=[CH:25][CH:26]=1)[N:23]=[CH:22][NH:21][C:20]2=[O:38]

Participants

7

Reactant 5

HCID 222AmmoniaHCID 11776TriphenylphosphineHCID 660484-Piperidinol, 1-methyl-HCID 97268Di-tert-butyl azodicarboxylateHCID 119748245-Hydroxy-6-methoxy-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-one

Product 1

HCID 1355106896-methoxy-5-(N-methylpiperidin-4-yloxy)-3,4-dihydroquinazolin-4-oneYield 62.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

A solution of di-tert-butyl azodicarboxylate (1.75 g ) in methylene chloride (3 ml) was added to a stirred mixture of 5-hydroxy-6-methoxy-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-one (1.55 g), triphenylphosphine (1.99 g), 4-hydroxy-1-methylpiperidine (0.75 g) and methylene chloride (12 ml) which had been cooled to 5° C. The mixture was stirred at ambient temperature for 1 hour. The mixture was evaporated and the residue was purified by column chromatography on silica using a 9:10:1 mixture of methylene chloride, ethyl acetate and a saturated methanolic ammonia solution as eluent. The material so obtained was stirred in a saturated methanolic ammonia solution for 48 hours. The mixture was evaporated and the residue was triturated under diethyl ether. The resultant solid was washed with diethyl ether and dried under vacuum to give 6-methoxy-5-(N-methylpiperidin-4-yloxy)-3,4-dihydroquinazolin-4-one (0.92 g); NMR Spectrum: (DMSOd6) 1.7–1.9 (m, 4H), 1.95 (t, 2H), 2.15 (s, 3H), 2.7 (m, 2H), 3.85 (s, 3H), 4.08 (m, 1H), 7.4 (d, 1H), 7.6 (d, 1H), 7.85 (s, 1H), 11.8 (br s, 1H); Mass Spectrum: M+H+ 290.

Workup

  1. customThe mixture was evaporated
  2. customthe residue was purified by column chromatography on silica using
  3. additiona 9:10:1 mixture of methylene chloride, ethyl acetate
  4. customThe material so obtained
  5. customThe mixture was evaporated
  6. customthe residue was triturated under diethyl ether
  7. washThe resultant solid was washed with diethyl ether
  8. customdried under vacuum

Sources & evidence

ORD record
ord-a1644463d5ea44138ce94219072d2d77
Source dataset
uspto-grants-2006_05
Patent number
US07049438B2

Reaction notes

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