Methanesulfonic Acid → HCID 54273189, compound

HRID 1378084Notes

Reaction equation

HRID 1378084 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:23])[N:9]3[CH2:22][CH2:21][CH2:20][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([NH:18][NH2:19])=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:24][CH2:25][C:26](OC(=O)CCl)=O.CS(O)(=O)=O.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[OH-].[Na+]>CN(C)C=O.CCOCC>[Cl:1][C:2]1[C:7]2[C:8](=[O:23])[N:9]3[CH2:22][CH2:21][CH2:20][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[O:17][C:26]([CH2:25][Cl:24])=[N:19][N:18]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6395Methanesulfonic AcidHCID 10946Chloroacetic anhydrideHCID 14798Sodium HydroxideHCID 14812Phosphorus oxide (P4O10)HCID 54008641HCID 54008641, compound

Product 1

HCID 54273189HCID 54273189, compoundYield 56.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of 3.06 g (9.22 mmol) of (S)-8-chloro-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2, 1-c][1,4]benzodiazepine-1-carboxylic acid hydrazide in 30 ml of N,N-dimethylformamide was treated with 1.97 g (0.0115 mol) of chloroacetic anhydride. The yellow solution obtained was stirred at room temperature for 11/2 hr. and then completely freed from the solvents. The residue was suspended in ether and filtered off under suction. The beige crystals obtained (3.75 g, m.p. 262°-264° (dec.)) were treated with 27 ml of methanesulphonic acid and 3 g of phosphorus pentoxide, whereupon the mixture was stirred at room temperature for 65 hrs. The orange-brown solution was poured into 150 ml of ice-water, made basic with aqueous sodium hydroxide solution and extracted with methylene chloride. The crystalline product was chromatographed over silica gel with ethyl acetate as the eluent. There were obtained 2.03 g (56%) of (S)-8-chloro-1-(5-chloromethyl-1,3,4-oxadiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one as white crystals; m.p. 230°-232° and [a]D20 =+104.5° (DMF, c=1%).

Workup

  1. customThe yellow solution obtained
  2. filtrationfiltered off under suction
  3. customThe beige crystals obtained (3.75 g, m.p. 262°-264° (dec.))
  4. stirringwas stirred at room temperature for 65 hrs
  5. extractionextracted with methylene chloride
  6. customThe crystalline product was chromatographed over silica gel with ethyl acetate as the eluent

Sources & evidence

ORD record
ord-339684fa9c8148ec811c4a88cffee08b
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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