4-Methylmorpholine → 2-Bromo-5-(3-chloro-4-fluoro-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

HRID 2204296Notes

Reaction equation

HRID 2204296 reaction equation
[Br:1][C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]([CH:10]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=2)[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[C:4]([C:27](O)=[O:28])[CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>O1CCOCC1.CCOC(C)=O>[Br:1][C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]2[CH:10]([C:11]3[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=3)[N:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([Cl:26])[CH:20]=3)[C:27](=[O:28])[C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867030995-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid

Product 1

HCID 867030982-Bromo-5-(3-chloro-4-fluoro-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid (Step D1) (1.483 mmol), HATU (1.632 mmol) and NMM (4.45 mmol) in dioxane (75 mL) was heated at 80° C. for 17 h. After cooling to rt, the reaction mixture was diluted with EtOAc and washed with a saturated aqueous solution of NaHCO3. The aqueous phase was extracted with EtOAc (2×). The combined organic phases were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as a light-yellow solid. tR: 5.31 min (HPLC 2); ESI-MS: tR=1.40 min, [M+H]+481/483/485 (LC-MS 1); TLC: Rf=0.27 (1:3 EtOAc/hexanes).

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with a saturated aqueous solution of NaHCO3
  3. extractionThe aqueous phase was extracted with EtOAc (2×)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified

Sources & evidence

ORD record
ord-90566a1bd14744df8e339bf9c173255d
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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