Carbon Dioxide → methyl (S)-3-hydroxy-2-(5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a]thieno[2,3-f][1,4]-diazepin-3-ylcarbonylamino)-propionate

HRID 1737393Notes

Reaction equation

HRID 1737393 reaction equation
[CH3:1][N:2]1[C:8](=[O:9])[C:7]2[S:10][CH:11]=[CH:12][C:6]=2[N:5]2[CH:13]=[N:14][C:15]([C:16]([OH:18])=O)=[C:4]2[CH2:3]1.C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.Cl.[CH3:35][O:36][C:37](=[O:42])[C@H:38]([CH2:40][OH:41])[NH2:39].C(N(CC)CC)C>CN(C)C=O>[OH:41][CH2:40][C@H:38]([NH:39][C:16]([C:15]1[N:14]=[CH:13][N:5]2[C:6]3[CH:12]=[CH:11][S:10][C:7]=3[C:8](=[O:9])[N:2]([CH3:1])[CH2:3][C:4]=12)=[O:18])[C:37]([O:36][CH3:35])=[O:42]

Participants

7

Reactant 5

HCID 280Carbon DioxideHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 2723730L-Serine, methyl ester, hydrochloride (1:1)HCID 212899275,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a]thieno[2,3-f][1,4]diazepine-3-carboxylic acid

Product 1

HCID 53755917methyl (S)-3-hydroxy-2-(5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a]thieno[2,3-f][1,4]-diazepin-3-ylcarbonylamino)-propionateYield 95.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 15.5 g (0.0493 mol) of 5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a]thieno[2,3-f][1,4]diazepine-3-carboxylic acid in 200 ml of dimethylformamide was treated portionwise with 8.07 g (0.0498 mol) of carbonyidiimidazole while gassing with argon. After completion of the CO2 evolution the mixture was stirred at 65° for 1 hr. After cooling to 0-5° the clear solution obtained was treated with 8.62 g (0.0554 mol) of L-serine methyl ester hydrochloride and with 12.3 ml (0.0554 mol) of triethylamine and stirred at room temperature for 16 hrs. The suspension was completely freed from the solvents. The residue was partitioned between water and ethyl acetate and extracted. The yellow oily residue was chromatographed over silica gel with ethyl acetate as the eluent. There were obtained 17.09 g (95%) of methyl (S)-3-hydroxy-2-(5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a]thieno[2,3-f][1,4]diazepin-3-ylcarbonylamino)-propionate as a yellowish oil. An analytical sample was recrystallized from ethyl acetate and gave white crystals; m.p. 158-160°. [α]D20 =+3.9° (CHCl3, c=1%).

Workup

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

Sources & evidence

ORD record
ord-dcaa284810b94608b3f3fefa286b40cb
Source dataset
uspto-grants-1999_10
Patent number
US05962450

Reaction notes

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