Formaldehyde → HCID 10301885, compound

HRID 1373325Notes

Reaction equation

HRID 1373325 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), 4.0–4.1 (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, 11, 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-df1ce6123216470d9900de0c6c318aff
Source dataset
uspto-grants-2007_01
Patent number
US07160891B2

Reaction notes

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