Methyl propiolate → HCID 20060995, compound

HRID 1085139Notes

Reaction equation

HRID 1085139 reaction equation
[NH2:1][C:2]1[CH2:3][C:4]([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[C:29]4[CH:28]=[CH:27][N:26]=[CH:25][C:24]=4[N:23]=[C:22]3[CH3:30])=[CH:17][CH:16]=2)=[N:5][C:6]2[CH:12]=[C:11]([CH3:13])[C:10]([CH3:14])=[CH:9][C:7]=2[N:8]=1.[C:31](OC)(=[O:34])[C:32]#[CH:33]>C(O)CCC>[CH3:13][C:11]1[C:10]([CH3:14])=[CH:9][C:7]2[N:8]3[CH:33]=[CH:32][C:31](=[O:34])[N:1]=[C:2]3[CH2:3][C:4]([C:15]3[CH:16]=[CH:17][C:18]([N:21]4[C:29]5[CH:28]=[CH:27][N:26]=[CH:25][C:24]=5[N:23]=[C:22]4[CH3:30])=[CH:19][CH:20]=3)=[N:5][C:6]=2[CH:12]=1

Participants

4

Reactant 2

HCID 13536Methyl propiolateHCID 10340604HCID 10340604, compound

Product 1

HCID 20060995HCID 20060995, compoundYield 10.3%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 2-amino-7,8-dimethyl-4-[4-(2-methylimidazo-[4,5-c]pyrid-1-yl)phenyl]-3H-[1,5]benzodiazepine (Example 44) (395 mg, 1.0 mmol) and methyl propiolate (168 mg, 2.0 mmol) in n-butanol (4 ml) was heated at reflux for 16 hours under nitrogen. The solvent was removed under reduced pressure and the residue was purified by flash chromatography (eluting with ethyl acetate:methanol: diethylamine=100:10:5). Fractions containing product were concentrated, and the residue was treated with dichloromethane, leaving some insoluble tarry material. The dichloromethane solution was decanted, concentrated, and the resulting brown solid triturated with hexane to give the title compound (46 mg, 10%), m.p. 192°-194° C.

Workup

  1. temperatureat reflux for 16 hours under nitrogen
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was purified by flash chromatography (eluting with ethyl acetate:methanol: diethylamine=100:10:5)
  4. additionFractions containing product
  5. concentrationwere concentrated
  6. additionthe residue was treated with dichloromethane
  7. customleaving some insoluble tarry material
  8. customThe dichloromethane solution was decanted
  9. concentrationconcentrated
  10. customthe resulting brown solid triturated with hexane

Sources & evidence

ORD record
ord-8634827d1e1f4e288d53a8f3db731ebb
Source dataset
uspto-grants-1991_04
Patent number
US05008263

Reaction notes

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