1,1,1-Trimethoxy-2-methylpropane → 4,5-dihydro-3-methyl-2-(1-methylethyl)-4-(3-methyl-2-thienyl)-3H-1,3-benzodiaze pine

HRID 486662

Reaction equation

HRID 486662 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH:9]([C:12]1[S:13][CH:14]=[CH:15][C:16]=1[CH3:17])[NH:10][CH3:11].[C:18](OC)(OC)(OC)[CH:19]([CH3:21])[CH3:20]>C(O)(=O)C>[CH3:11][N:10]1[CH:9]([C:12]2[S:13][CH:14]=[CH:15][C:16]=2[CH3:17])[CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[N:1]=[C:18]1[CH:19]([CH3:21])[CH3:20]

Participants

4

Reactant 2

HCID 404951,1,1-Trimethoxy-2-methylpropaneHCID 130176Compound 7189

Product 1

HCID 224143684,5-dihydro-3-methyl-2-(1-methylethyl)-4-(3-methyl-2-thienyl)-3H-1,3-benzodiaze pineYield 26.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 5.86 g of 2-amino-N-methyl-α-(3-methyl-2-thienyl)benzeneethanamine and 19.56 g of trimethyl orthoisobutyrate was treated rapidly with 7.94 ml of glacial acetic acid. The solution was refluxed for 8 hours under nitrogen and concentrated on a rotary evaporator at 40° C. The residual oil was acidified with 10% hydrochloric acid solution and extracted with ether (3×100 ml). The aqueous phase was basified with 10% sodium hydroxide solution and extracted with dichloromethane (3×100 ml). The organic phases was dried over anhydrous sodium sulfate, filtered and concentrated to an oil. Purification was accomplished by HPLC (Water's Associates Prep LC/System 500A, silica gel, utilizing methanol followed by 2% triethylamine in methanol as successive eluents). Concentration of the appropriate fractions yielded 1.88 g of 4,5-dihydro-3-methyl-2-(1-methylethyl)-4-(3-methyl-2-thienyl)-3H-1,3-benzodiaze pine as an oil. The oil was treated with ethereal hydrogen chloride and the resulting precipitate was triturated with ether to yield 1.80 g of 4,5-dihydro-3-methyl-2-(1-methylethyl)-4-(3-methyl-2-thienyl)-3H-1,3-benzodiazepine hydrochloride, mp 240.5°-241.0° C.

Workup

  1. temperatureThe solution was refluxed for 8 hours under nitrogen
  2. concentrationconcentrated on a rotary evaporator at 40° C
  3. extractionextracted with ether (3×100 ml)
  4. extractionextracted with dichloromethane (3×100 ml)
  5. dry with materialThe organic phases was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to an oil
  8. customPurification

Sources & evidence

ORD record
ord-b6765f9da7d24cc9be5113b1aaa3f37a
Source dataset
uspto-grants-1994_03
Patent number
US05292760

Linked notes

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