Boron tribromide → HCID 67355200, compound

HRID 525177Notes

Reaction equation

HRID 525177 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][C@@H:14]3[CH2:18][CH2:17][N:16]([C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:24])=[C:4]([O:25]C)[CH:3]=1.B(Br)(Br)Br>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][C@@H:14]3[CH2:18][CH2:17][N:16]([C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:24])=[C:4]([OH:25])[CH:3]=1

Participants

3

Reactant 2

HCID 25134Boron tribromideHCID 67376193HCID 67376193, compound

Product 1

HCID 67355200HCID 67355200, compound

Conditions

Temperature
0 °C

Procedure

To a microwave vial was added 4-[4-bromo-2-(methyloxy)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (132 mg, 0.313 mmol) and the solid was purged with nitrogen. Dichloromethane (1.5 mL) was added to the solid and was cooled to 0° C. Boron tribromide (2.037 mL, 2.037 mmol, 1M in dichloromethane) was added to the cooled solution and allowed to warm to room temperature. Analysis by LCMS indicated the presence of desired product and starting material. The solution was re-cooled to 0° C. and slowly treated with another portion of boron tribromide (2.037 mL, 2.037 mmol, 1M in dichloromethane). Analysis by LCMS indicated the consumption of starting material and presence of desired product. The solution was concentrated, dissolved in 2 mL dimethylsulfoxide, and purified by reverse phase HPLC (10-90% acetonitrile/water with 0.1% TFA). The desired fractions were collected and added to a separatory funnel containing ethyl acetate. The aqueous phase was adjusted to pH˜6 with 1N aq HCl. The aqueous phase was extracted with ethyl acetate (3×), and the combined organics were washed with brine, dried over sodium sulfate, and concentrated in vacuo to afford the title product as a white solid (95 mg, 75%). MS(ES)+ m/e 407.1, 409.0 M+H]+.

Workup

  1. customthe solid was purged with nitrogen
  2. additionDichloromethane (1.5 mL) was added to the solid
  3. temperatureto warm to room temperature

Sources & evidence

ORD record
ord-9bac8fda6b0f419993500184a3cbc25c
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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