Allyl bromide → (S)-1-(3-diallylaminomethyl-1,2,4-oxadiazol-5-yl)-8-chloro-7-fluoro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

HRID 1378058Notes

Reaction equation

HRID 1378058 reaction equation
[NH2:1][CH2:2][C:3]1[N:7]=[C:6]([C:8]2[N:9]=[CH:10][N:11]3[C:17]4[CH:18]=[CH:19][C:20]([F:23])=[C:21]([Cl:22])[C:16]=4[C:15](=[O:24])[N:14]4[CH2:25][CH2:26][C@H:13]4[C:12]=23)[O:5][N:4]=1.[CH2:27](Br)[CH:28]=[CH2:29].C(N(C(C)C)[CH:34]([CH3:36])[CH3:35])C>C(Cl)Cl>[CH2:27]([N:1]([CH2:2][C:3]1[N:7]=[C:6]([C:8]2[N:9]=[CH:10][N:11]3[C:17]4[CH:18]=[CH:19][C:20]([F:23])=[C:21]([Cl:22])[C:16]=4[C:15](=[O:24])[N:14]4[CH2:25][CH2:26][C@H:13]4[C:12]=23)[O:5][N:4]=1)[CH2:36][CH:34]=[CH2:35])[CH:28]=[CH2:29]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 81531DiisopropylethylamineHCID 53728112(S)-1-(3-aminomethyl-1,2,4-oxadiazol-5-yl)-8-chloro-7-fluoro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

Product 1

HCID 54350834(S)-1-(3-diallylaminomethyl-1,2,4-oxadiazol-5-yl)-8-chloro-7-fluoro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-oneYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

11.7 g (31.2 mmol) of crude (S)-1-(3-aminomethyl-1,2,4-oxadiazol-5-yl)-8-chloro-7-fluoro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one, 100 ml of methylene chloride, 6.04 g (50 mmol) of allyl bromide and 7.75 g (60 mmol) of N-ethyldiisopropylamine were stirred at room temperature overnight. The solution was concentrated and the residue was purified by chromatography on 500 g of silica gel while eluting with ethyl acetate. After recrystallization from methanol there were obtained 5.3 g (47%) of (S)-1-(3-diallylaminomethyl-1,2,4-oxadiazol-5-yl)-8-chloro-7-fluoro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of m.p. 139°-140°, which was converted into the hydrochloride of m.p. 127°.

Workup

  1. concentrationThe solution was concentrated
  2. customthe residue was purified by chromatography on 500 g of silica gel
  3. washwhile eluting with ethyl acetate
  4. customAfter recrystallization from methanol

Sources & evidence

ORD record
ord-8983435025ff409db9de1f35decd1387
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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