Boron tribromide → 2-[(4S)-6-(4-chlorophenyl)-8-hydroxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide

HRID 1526677Notes

Reaction equation

HRID 1526677 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([O:19]C)[CH:17]=[CH:18][C:13]=3[N:12]3[C:21]([CH3:24])=[N:22][N:23]=[C:11]3[C@H:10]([CH2:25][C:26]([NH:28][CH2:29][CH3:30])=[O:27])[N:9]=2)=[CH:4][CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([OH:19])[CH:17]=[CH:18][C:13]=3[N:12]3[C:21]([CH3:24])=[N:22][N:23]=[C:11]3[C@H:10]([CH2:25][C:26]([NH:28][CH2:29][CH3:30])=[O:27])[N:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 469434322-[(4S)-6-(4-Chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide2×

Product 1

HCID 529354812-[(4S)-6-(4-chlorophenyl)-8-hydroxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

2-[(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide (which may be prepared, for example, by reaction of Reference compound H with ethylamine) (0.424 g) was dissolved in DCM (8 ml) and cooled to −78° C. A solution of boron tribromide (0.945 ml) in DCM (2 ml) was added slowly to the reaction mixture. The reaction was stirred at −78° C. for 35 min under nitrogen and then at room temperature for 2.5 h. The reaction was quenched by adding a solution of ethanol (1 ml) in DCM (5 ml) dropwise. The solvent was evaporated and the residue was chromatographed (0-10% methanol:DCM) to give 2-[(4S)-6-(4-chlorophenyl)-8-hydroxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide as a yellow solid. The aqueous layer was passed through a pre equilibrated Biotage 103 column, the organic content was eluted with methanol and the methanolic solution was evaporated to give a further quantity of 2-[(4S)-6-(4-chlorophenyl)-8-hydroxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide as a yellow solid (total yield 271.3 mg).

Workup

  1. waitat room temperature for 2.5 h
  2. customThe reaction was quenched
  3. additionby adding a solution of ethanol (1 ml) in DCM (5 ml) dropwise
  4. customThe solvent was evaporated
  5. customthe residue was chromatographed (0-10% methanol:DCM)

Sources & evidence

ORD record
ord-d4fd6534cbc74f94842b5c2a7e98573b
Source dataset
uspto-grants-2015_07
Patent number
US09085582B2

Reaction notes

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