Trimethyl orthoformate → HCID 86672704, compound

HRID 2168522Notes

Reaction equation

HRID 2168522 reaction equation
[NH2:1][C:2]1[C:3]([NH:12][CH2:13][CH:14]([O:17][CH3:18])[O:15][CH3:16])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH:19](OC)(OC)OC>CN(C=O)C>[CH3:16][O:15][CH:14]([O:17][CH3:18])[CH2:13][N:12]1[C:3]2[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=[CH:11][C:2]=2[N:1]=[CH:19]1

Participants

4

Reactant 2

HCID 9005Trimethyl orthoformateHCID 66889618HCID 66889618, compound

Product 1

HCID 86672704HCID 86672704, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 3-amino-2-(2,2-dimethoxyethylamino)benzoate (0.4 g, 1.6 mmol) from Step C above in DMF (15 mL) was added trimethyl orthoformate (0.5 mL, 4.7 mmol) and the reaction was heated to reflux and stirred overnight. The reaction mixture was washed with water, extracted with methylene chloride, dried (Na2SO4), filtered, and concentrated under reduced pressure to give the crude material which was purified by column chromatography (silica gel, 0% to 100% ethyl acetate in hexanes) to afford methyl 1-(2,2-dimethoxyethyl)-1H-benzo[d]imidazole-7-carboxylate: 1H NMR (500 MHz, DMSO-d6) δ 8.25 (s, 1H), 7.90 (dd, J=8.0, 1.0 Hz, 1H), 7.69 (dd, J=8.0, 1.0 Hz, 1H), 7.29 (t, J=8.0 Hz, 1H), 4.64 (d, J=5.0 Hz, 2H), 4.48 (t, J=5.0 Hz, 1H), 3.91 (s, 3H), 3.22 (s, 6H); MS (ESI+) m/z 264 (M+H).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux
  3. washThe reaction mixture was washed with water
  4. extractionextracted with methylene chloride
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude material which
  9. customwas purified by column chromatography (silica gel, 0% to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c5455ef5b9dc4652bc1a09d71c24e1bf
Source dataset
uspto-grants-2015_06
Patent number
US09045501B2

Reaction notes

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