Triethylamine → HCID 59369751, compound

HRID 1807079Notes

Reaction equation

HRID 1807079 reaction equation
[Cl:1][C:2]1[C:3]([F:39])=[C:4]([C@@H: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])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[O:35][C:34]([C:36](O)=[O:37])=[CH:33][CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1.[NH4+].[Cl-].CC[N:44]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>CN(C)C=O>[Cl:1][C:2]1[C:3]([F:39])=[C:4]([C@@H: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])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:25])[CH3:26])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[O:35][C:34]([C:36]([NH2:44])=[O:37])=[CH:33][CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 59369759HCID 59369759, compound

Product 1

HCID 59369751HCID 59369751, compoundYield 52.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of rac-5-{[(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-carbonyl]-amino}-furan-2-carboxylic acid prepared in Example 145 (60 mg, 0.1 mmol) in N,N-dimethylformamide (2 mL) was added NH4Cl (28 mg, 0.5 mmol), EDCI (40 mg, 0.2 mmol), HOBT (28 mg, 0.2 mmol) and NEt3 (0.029 mL, 0.2 mmol). The reaction mixture was heated at 75° C. for 20 h. The mixture was cooled to room temperature, and partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (EtOAc) to give rac-5-{[(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-carbonyl]-amino}-furan-2-carboxylic acid amide as a white solid (30 mg, 50%).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washwashed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography (EtOAc)

Sources & evidence

ORD record
ord-8408b610bb734cc98f6205cd6aa2d8a0
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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