Formaldehyde → HCID 10301885, compound

HRID 641773Notes

Reaction equation

HRID 641773 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:25]=[C:24]3[C:19]([C:20]([NH:26][C:27]4[C:32]([Cl:33])=[CH:31][CH:30]=[C:29]5[O:34][CH2:35][O:36][C:28]=45)=[N:21][CH:22]=[N:23]3)=[C:18]([O:37][CH:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C=O>C(O)=O>[Cl:33][C:32]1[C:27]([NH:26][C:20]2[C:19]3[C:24](=[CH:25][C:16]([O:15][CH2:14][CH:11]4[CH2:10][CH2:9][N:8]([CH3:6])[CH2:13][CH2:12]4)=[CH:17][C:18]=3[O:37][CH:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)[N:23]=[CH:22][N:21]=2)=[C:28]2[O:36][CH2:35][O:34][C:29]2=[CH:30][CH:31]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 11975065HCID 11975065, compound

Product 1

HCID 10301885HCID 10301885, compoundYield 46.5%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 7-[N-(tert-butoxycarbonyl)piperidin-4-ylmethoxy]-4-(6-chloro-2,3-methylenedioxyanilino)-5-tetrahydropyran-4-yloxyquinazoline (0.25 g), a concentrated aqueous formaldehyde solution (37%, 0.5 ml) and formic acid (5 ml) was stirred and heated to 100° C. for 2 hours. The mixture was cooled to ambient temperature and evaporated. The residue was purified by column chromatography on silica using a 24:1 mixture of methylene chloride and a saturated methanolic ammonia solution as eluent. The material so obtained was partitioned between methylene chloride and an aqueous ammonium hydroxide solution. The organic layer was dried over magnesium sulphate and evaporated. There was thus obtained the title compound (0.1 g); NMR Spectrum: (CDCl3) 1.4-1.6 (m, 2H), 1.75-1.9 (m, 3H), 1.9-2.1 (m, 4H), 2.2-2.3 (m, 2H), 2.29 (s, 3H), 2.9 (d, 2H), 3.6-3.7 (m, 2H), 3.95 (d, 2H), 4.04.1 (m, 2H), 4.75 (m, 1H), 6.05 (s, 2H), 6.5 (d, 1H), 6.72 (d, 1H), 6.81 (d, 1H), 6.97 (d, 1H), 8.5 (s, 1H), 9.26 (s, 1H); Mass Spectrum: M+H+ 527 and 529.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customevaporated
  3. customThe residue was purified by column chromatography on silica using
  4. additiona 24:1 mixture of methylene chloride
  5. customThe material so obtained
  6. customwas partitioned between methylene chloride
  7. dry with materialThe organic layer was dried over magnesium sulphate
  8. customevaporated

Sources & evidence

ORD record
ord-7a52c0424ab64b588bca77a0ae0a972d
Source dataset
uspto-grants-2010_04
Patent number
US07696214B2

Reaction notes

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