Trimethyl orthoformate → HCID 68516158, compound

HRID 2241187Notes

Reaction equation

HRID 2241187 reaction equation
[CH3:1]OC(OC)OC.[CH3:8][C:9]1([CH3:17])[O:14][C:13](=[O:15])[CH2:12][C:11](=[O:16])[O:10]1.[CH3:18][O:19][C:20]1[CH:33]=[CH:32][C:23]([CH2:24][N:25]2[C:29]([NH2:30])=[CH:28][C:27]([CH3:31])=[N:26]2)=[CH:22][CH:21]=1>>[CH3:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:24][N:25]2[C:29]([NH:30][CH:1]=[C:12]3[C:13](=[O:15])[O:14][C:9]([CH3:17])([CH3:8])[O:10][C:11]3=[O:16])=[CH:28][C:27]([CH3:31])=[N:26]2)=[CH:32][CH:33]=1

Participants

4

Reactant 3

HCID 9005Trimethyl orthoformate2×HCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 233777491-[(4-Methoxyphenyl)methyl]-3-methyl-1H-pyrazol-5-amine

Product 1

HCID 68516158HCID 68516158, compound

Procedure

A stirred mixture of trimethoxymethane (118 mL, 1077 mmol) and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) (15.5 g, 108 mmol) was heated under reflux for 1 hour. A suspension of 1-(4-methoxybenzyl)-3-methyl-1H-pyrazol-5-amine (23.4 g, 108 mmol; prepared according to the procedure described by Misra, R. N.; et al. Bioorg. Med. Chem. Lett. 2003, 13, 1133-1136) in trimethyl orthoformate (110 mL, 1075 mmol) was added at once, and the dark orange reaction was refluxed for 3 hours under N2. After cooling to room temperature, the reaction was concentrated in vacuo, using toluene (3×100 mL) to azeotrope residual trimethyl orthoformate. The resulting deep orange residue was triturated/sonicated with diethyl ether (200 mL). The resulting peach colored solid was filtered, washing with diethyl ether (3×50 mL). Yield: 28.0 g, 70%. 1H NMR (400 MHz, DMSO-d6) δ 11.13 (d, J=11 Hz, 1H), 8.06 (d, J=11 Hz, 1H), 7.10 (d, J=9 Hz, 2H), 6.87 (d, J=9 Hz, 2H), 6.32 (s, 1H), 5.19 (s, 2H), 3.70 (s, 3H), 2.14 (s, 3H), 1.65 (s, 6H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 1 hour
  3. customprepared
  4. customthe dark orange reaction
  5. temperaturewas refluxed for 3 hours under N2
  6. concentrationthe reaction was concentrated in vacuo
  7. customThe resulting deep orange residue was triturated/sonicated with diethyl ether (200 mL)
  8. filtrationThe resulting peach colored solid was filtered
  9. washwashing with diethyl ether (3×50 mL)

Sources & evidence

ORD record
ord-61370a77552e4207b70fe59e8aa01507
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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