Carbon Dioxide → HCID 53816448, compound

HRID 1737386Notes

Reaction equation

HRID 1737386 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([CH3:19])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([OH:18])=O)[C:6]=2[CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.Cl.[CH3:37][O:38][C:39](=[O:44])[C@H:40]([CH2:42][OH:43])[NH2:41].C(N(CC)CC)C>CN(C)C=O>[Cl:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([CH3:19])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([NH:41][C@@H:40]([CH2:42][OH:43])[C:39]([O:38][CH3:37])=[O:44])=[O:18])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 280Carbon DioxideHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 2723730L-Serine, methyl ester, hydrochloride (1:1)HCID 145904217-chloro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid

Product 1

HCID 53816448HCID 53816448, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 14.1 g (0.0484 mol) of 7-chloro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid in 150 ml of dimethylformamide was treated portionwise with 8.24 g (0.0508 mol). of carbonyidiimidazole while gassing with argon. After completion of the CO2 evolution the mixture was stirred at 65° for 3 hrs. After cooling to 0-5° the white suspension obtained was treated with 8.28 g (0.0532 mol) of L-serine methyl ester hydrochloride and with 7.452 ml (0.0532 mol) of triethylamine and stirred at room temperature for 21 hrs. The white suspension was suction filtered and the filtrate was completely freed from the solvents. The orange oily residue was partitioned between ethyl acetate and water, extracted, chromatographed over silica gel with ethyl acetate/ethanol 9:1 as the eluent and recrystallized from hot ethyl acetate; the mother liquor was then digested with diethyl ether. There were obtained a total of 14.0 g (74%) of methyl (S)-2-(7-chloro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-3-ylcarbonylamino)-3-hydroxy-propionate as white crystals; m.p. 178-180°. [α]D20 =+1.2° (CH2Cl2, c=1%).

Workup

  1. additionwas treated portionwise with 8.24 g (0.0508 mol)
  2. temperatureAfter cooling to 0-5° the white suspension
  3. customobtained
  4. filtrationsuction filtered
  5. customThe orange oily residue was partitioned between ethyl acetate and water
  6. extractionextracted
  7. customchromatographed over silica gel with ethyl acetate/ethanol 9:1 as the eluent
  8. customrecrystallized from hot ethyl acetate

Sources & evidence

ORD record
ord-7c76d9eff0d54c35ac2ff73c5f48d784
Source dataset
uspto-grants-1999_10
Patent number
US05962450

Reaction notes

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