Carbon Dioxide → HCID 86753964, compound

HRID 1737381Notes

Reaction equation

HRID 1737381 reaction equation
[CH3:1][N:2]1[C:8](=[O:9])[C:7]2[CH:10]=[CH:11][CH:12]=[CH:13][C:6]=2[N:5]2[CH:14]=[N:15][C:16]([C:17]([OH:19])=O)=[C:4]2[CH2:3]1.C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.Cl.[CH3:36][O:37][C:38](=[O:43])[C@H:39]([CH2:41][OH:42])[NH2:40].C(N(CC)CC)C>CN(C)C=O.O>[OH:42][CH2:41][C@H:39]([NH:40][C:17]([C:16]1[N:15]=[CH:14][N:5]2[C:6]3[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=3[C:8](=[O:9])[N:2]([CH3:1])[CH2:3][C:4]=12)=[O:19])[C:38]([O:37][CH3:36])=[O:43]

Participants

8

Reactant 5

HCID 280Carbon DioxideHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 2723730L-Serine, methyl ester, hydrochloride (1:1)HCID 103326765-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid

Product 1

HCID 86753964HCID 86753964, compoundYield 68.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of 11.3 g (0.0437 mol) of 5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid in 220 ml of dimethylformamide was treated portionwise with 7.80 g (0.048 mol) of carbonyldiimidazole while gassing with argon. After completion of the CO2 evolution the mixture was stirred at 55° for 2 hrs. After cooling to 0-5° the pale yellow solution obtained was treated with 7.48 g (0.0532 mol) of L-serine methyl ester hydrochloride and with 6.7 ml (0.048 mol) of triethylamine and stirred at room temperature for 70 hrs. The light suspension was completely freed from the solvents. The residue was dissolved in hot water and extracted continuously with ethyl acetate. The yellow oily residue was chromatographed over silica gel with ethyl acetate as the eluent. There were obtained 10.7 g (68%) of methyl (S)-3-hydroxy-2-(5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-3-ylcarbonylamino)-propionate as a white solid. An analytical sample was recrystallized from ethyl acetate/diethyl ether and gave white crystals; m.p. 180-181°. [α]D20 =+12.9° (CHCl3, c=1%).

Workup

  1. temperatureAfter cooling to 0-5° the pale yellow solution
  2. customobtained
  3. extractionextracted continuously with ethyl acetate
  4. customThe yellow oily residue was chromatographed over silica gel with ethyl acetate as the eluent

Sources & evidence

ORD record
ord-db3a6393e2554e818afd23ddb0d16ad6
Source dataset
uspto-grants-1999_10
Patent number
US05962450

Reaction notes

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