Dichloromethane → HCID 59249648, compound

HRID 1807128Notes

Reaction equation

HRID 1807128 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]2C(O)=O)[CH:5]=[CH:6][CH:7]=1.CN([C:35]([O:39]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN([CH:62]([CH3:64])[CH3:63])C(C)C.[NH2:65][CH:66](C(C)(C)C)[C:67]([O-:69])=[O:68].[CH2:74](Cl)Cl>>[C:62]([O:69][C:67](=[O:68])[CH2:66][NH:65][C:35]([C@H:9]1[C@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:31])[C@:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[NH:10]1)=[O:39])([CH3:64])([CH3:74])[CH3:63]

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18448917HCID 18448917, compoundHCID 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 59249648HCID 59249648, compound

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 (515 mg, 1.11 mmol) in methylene chloride (10 mL), HATU (Aldrich, 422 mg, 1.11 mmol) was added followed by the addition of DIPEA (0.5 mL) and 2-amino-t-butyl-acetate (Aldrich, 145 mg, 1.11 mmol). The mixture was stirred at rt for 2 hrs. 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 (40 g column, eluent, 30% EtOAc/hexanes chloride) to give a white solid. 510 mg.

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 (40 g column, eluent, 30% EtOAc/hexanes chloride)
  6. customto give a white solid

Sources & evidence

ORD record
ord-69b772ce2a1c4247876a233b0f46d7ed
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

Loading…