N-bromobutanimide → HCID 86703241, compound

HRID 2204420Notes

Reaction equation

HRID 2204420 reaction equation
C1C(=O)N([Br:8])C(=O)C1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[C:20]3[N:21]([CH:24]4[CH2:26][CH2:25]4)[CH:22]=[CH:23][C:19]=3[C:18](=[O:27])[N:17]2[C:28]2[CH:33]=[C:32]([CH3:34])[C:31](=[O:35])[N:30]([CH3:36])[CH:29]=2)=[CH:12][CH:11]=1>C(Cl)(Cl)(Cl)Cl.C(Cl)Cl>[Br:8][C:22]1[N:21]([CH:24]2[CH2:26][CH2:25]2)[C:20]2[CH:16]([C:13]3[CH:14]=[CH:15][C:10]([Cl:9])=[CH:11][CH:12]=3)[N:17]([C:28]3[CH:33]=[C:32]([CH3:34])[C:31](=[O:35])[N:30]([CH3:36])[CH:29]=3)[C:18](=[O:27])[C:19]=2[CH:23]=1

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 86703242HCID 86703242, compound

Product 1

HCID 86703241HCID 86703241, compoundYield 70.9%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 6344DichloromethaneSolvent

Procedure

NBS (0.497 g, 2.79 mmol) was added to a mixture of 6-(4-chlorophenyl)-1-cyclopropyl-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (Step 240.2) (1.1 g, 2.79 mmol) in CCl4 (40 mL) at 0° C. The reaction mixture was stirred for 40 h at rt, concentrated, diluted with EtOAc/water, and extracted twice with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), and concentrated. The crude product was purified by silica gel column chromatography (CH2Cl2/MeOH 95:5) to afford a white solid and mixed fractions. The mixed fractions were purified by SFC (column 2-EP 250×30 mm, 5 μm, 60 Å, Princeton; flow 100 mL/min; gradient: isocratic 5% B for 25 min; A: scCO2, B: MeOH) to afford a white solid. Both solids were dissolved in CH2Cl2 and concentrated to afford the title compound (935 mg, 70.8% yield) as a white solid. tR: 1.07 min (LC-MS 6); ESI-MS: 472.1/474.1 [M+H]+ (LC-MS 6); TLC (CH2Cl2/MeOH 95:5): Rf=0.27.

Workup

  1. concentrationconcentrated
  2. additiondiluted with EtOAc/water
  3. extractionextracted twice with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel column chromatography (CH2Cl2/MeOH 95:5)
  8. customto afford a white solid
  9. additionmixed fractions
  10. customThe mixed fractions were purified by SFC (column 2-EP 250×30 mm, 5 μm, 60 Å, Princeton
  11. waitgradient: isocratic 5% B for 25 min
  12. customA: scCO2, B: MeOH) to afford a white solid
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-ca3ca81a79e74dec80a8d00503a3623b
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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