Boron tribromide → HCID 73052775, compound

HRID 2275043Notes

Reaction equation

HRID 2275043 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([C:10]2[CH:32]=[CH:31][C:13]3[N:14]([CH3:30])[C:15]([C:17]4[N:27]([CH2:28][CH3:29])[C:20]5=[N:21][CH:22]=[C:23]([O:25]C)[CH:24]=[C:19]5[CH:18]=4)=[N:16][C:12]=3[CH:11]=2)=[O:9])[CH2:3]1.B(Br)(Br)Br>ClCCl.CS(C)=O>[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([C:10]2[CH:32]=[CH:31][C:13]3[N:14]([CH3:30])[C:15]([C:17]4[N:27]([CH2:28][CH3:29])[C:20]5=[N:21][CH:22]=[C:23]([OH:25])[CH:24]=[C:19]5[CH:18]=4)=[N:16][C:12]=3[CH:11]=2)=[O:9])[CH2:3]1

Participants

5

Reactant 2

HCID 25134Boron tribromideHCID 90027034HCID 90027034, compound

Product 1

HCID 73052775HCID 73052775, compoundYield 114.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-(3-aminopiperidin-1-yl)(2-(1-ethyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (11 mg, 0.025 mmol) in dichloromethane (DCM) (3 mL) was cooled to 0° C. using an ice-water bath under nitrogen. Boron tribromide (8 μL, 0.085 mmol) was added to the reaction dropwise with vigorous stirring. The reaction mixture was allowed to return to room temperature with stirring, over 4 hours. The reaction mixture was partitioned with water (5 mL), the organic layer was isolated using a hydrophobic frit, and the aqueous layer was re-extracted with DCM (2×10 mL). The combined organic layers were evaporated in vacuo but LCMS showed there was no product. The aqueous layer was neutralised by the dropwise addition of NaHCO3, partitioned with DCM and separated. The aqueous was re-extracted with DCM (2×15 mL) and the combined organic layers were concentrated in vacuo to give the crude product. The residue was dissolved in DMSO 1 mL and purified by MDAP with an ammonium bicarbonate modifier (Method E). The appropriate fraction was evaporated in vacuo to give the title compound as a yellow gum (12 mg).

Workup

  1. customto return to room temperature
  2. customThe reaction mixture was partitioned with water (5 mL)
  3. customthe organic layer was isolated
  4. extractionthe aqueous layer was re-extracted with DCM (2×10 mL)
  5. customThe combined organic layers were evaporated in vacuo but LCMS
  6. additionThe aqueous layer was neutralised by the dropwise addition of NaHCO3
  7. custompartitioned with DCM
  8. customseparated
  9. extractionThe aqueous was re-extracted with DCM (2×15 mL)
  10. concentrationthe combined organic layers were concentrated in vacuo
  11. customto give the crude product
  12. custompurified by MDAP with an ammonium bicarbonate modifier (Method E)
  13. customThe appropriate fraction was evaporated in vacuo

Sources & evidence

ORD record
ord-2e7189e2a6b941a1a7261480445667af
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

Loading…