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

HRID 2204291Notes

Reaction equation

HRID 2204291 reaction equation
[Cl:1][C:2]1[C:3]([F:29])=[C:4]([NH:8][CH:9]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=2[CH3:28])[C:10]2[N:11]([CH:18]([CH3:20])[CH3:19])[CH:12]=[CH:13][C:14]=2[C:15]([OH:17])=O)[CH:5]=[CH:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[C:3]([F:29])=[C:4]([N:8]2[C:15](=[O:17])[C:14]3[CH:13]=[CH:12][N:11]([CH:18]([CH3:20])[CH3:19])[C:10]=3[CH:9]2[C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=2[CH3:28])[CH:5]=[CH:6][CH:7]=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 867030942-[(3-chloro-2-fluoro-phenylamino)-(4-chloro-2-methyl-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid

Product 1

HCID 867030935-(3-chloro-2-fluoro-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-[(3-chloro-2-fluoro-phenylamino)-(4-chloro-2-methyl-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid (Step A2) (2.257 mmol), HATU (2.482 mmol) and NMM (6.77 mmol) in DMF (30 mL) was heated at 80° C. for 18 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 white solid. tR: 5.31 min (HPLC 1); ESI-MS: tR=1.29 min, [M+H]+ 417/419 (LC-MS 1); TLC: Rf=0.13 (1:3 EtOAc/heptanes).

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-f87116c44487467e8ddeae655ebed326
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

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