Dipropylamine → (S)-8-chloro-1-(4-dipropylaminomethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo-[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

HRID 1737364Notes

Reaction equation

HRID 1737364 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[S:17][CH:18]=[C:19]([CH2:21]Cl)[N:20]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH2:27]([NH:30][CH2:31][CH2:32][CH3:33])[CH2:28][CH3:29]>O1CCCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[S:17][CH:18]=[C:19]([CH2:21][N:30]([CH2:31][CH2:32][CH3:33])[CH2:27][CH2:28][CH3:29])[N:20]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 8902DipropylamineHCID 70067673(S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

Product 1

HCID 70067101(S)-8-chloro-1-(4-dipropylaminomethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo-[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-oneYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1.0 g (0.0025 mol) of (S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one in 20 ml of tetrahydrofuran was treated with 5 ml (0.037 mol) of dipropylamine and stirred at 50° for 96 hrs. All volatiles were removed in a waterjet vacuum and the residue was taken up with ethyl acetate and water. The organic phase was dried over magnesium sulphate, concentrated and the residue remaining was chromatographed over silica gel with methylene chloride/methanol 95:5 as the eluent. After recrystallization from ethyl acetate there was obtained 0.67 g (58%) of (S)-8-chloro-1-(4-dipropylaminomethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one in the form of white crystals; m.p. 213-214° and [α]D20 =-68.5° (MeOH, c=0.8%).

Workup

  1. customAll volatiles were removed in a waterjet vacuum
  2. dry with materialThe organic phase was dried over magnesium sulphate
  3. concentrationconcentrated
  4. customthe residue remaining was chromatographed over silica gel with methylene chloride/methanol 95:5 as the eluent
  5. customAfter recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-d83be46409bb4d95aa4d55f0fcc78eaa
Source dataset
uspto-grants-1999_10
Patent number
US05962450

Reaction notes

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