3-Aminobenzamide → HCID 59249445, compound

HRID 1807152Notes

Reaction equation

HRID 1807152 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][CH:9]2[C:28](O)=[O:29])[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.CCN(C(C)C)C(C)C.[NH2:65][C:66]1[CH:67]=[C:68]([CH:72]=[CH:73][CH:74]=1)[C:69]([NH2:71])=[O:70]>C(Cl)Cl.CO>[C:69]([C:68]1[CH:67]=[C:66]([NH:65][C:28]([C@H:9]2[C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:31])[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])[NH:10]2)=[O:29])[CH:74]=[CH:73][CH:72]=1)(=[O:70])[NH2:71]

Participants

7

Reactant 4

HCID 16453-AminobenzamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666882513-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid

Product 1

HCID 59249445HCID 59249445, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of rac (2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (100 mg, 0.172 mmol) in methylene chloride (10 mL), HATU (Aldrich, 98 mg, 0.258 mmol) was added followed by the addition of DIPEA (90 uL, 0.52 mmol) and 3-amino benzamide (Oakwood, 35 mg, 0.26 mmol). The mixture was stirred at rt overnight. The reaction was quenched with addition of water. The mixture was extracted with methylene chloride (2×10 mL) and the extracts were dried with magnesium sulfate. The solvent was removed and the residue was purified on an ISCO machine (24 g column, eluent, 30% EtOAc/methylene chloride) to give a white solid. 58 mg. The solid was resolved on a Berger SFC system on a Whelk column under 100 bar, 30° C., and 35% of methanol to give two peaks: Peak 1, undesired enantiomer, 19 mg; Peak 2, 21 mg as white solid.

Workup

  1. customThe reaction was quenched with addition of water
  2. extractionThe mixture was extracted with methylene chloride (2×10 mL)
  3. dry with materialthe extracts were dried with magnesium sulfate
  4. customThe solvent was removed
  5. customthe residue was purified on an ISCO machine (24 g column, eluent, 30% EtOAc/methylene chloride)
  6. customto give a white solid
  7. customto give two peaks

Sources & evidence

ORD record
ord-a55b42d2be2841c28e2f405a9ad3cb72
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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