Triethylamine → HCID 59369764, compound

HRID 1807077Notes

Reaction equation

HRID 1807077 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.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH2:45][C:46]1[O:50][C:49]([C:51]([O:53][CH3:54])=[O:52])=[CH:48][CH:47]=1>ClCCl.CN(C1C=CN=CC=1)C.O.CN(C=O)C>[CH3:54][O:53][C:51]([C:49]1[O:50][C:46]([NH:45][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:47][CH:48]=1)=[O:52]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 5072225Methyl 5-aminofuran-2-carboxylateHCID 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 59369764HCID 59369764, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 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 (0.5 g, 1.07 mmol) in dichloromethane (5 mL) at 0° C. was added oxalyl chloride (0.11 mL, 1.28 mmol) and DMF (0.03 mL). The reaction mixture was stirred at 0° C. for 3 h, then concentrated. The residue was dissolved into dichloromethane (5 mL), triethylamine (0.45 mL, 3.2 mmol) and DMAP (20 mg, 0.14 mmol) were added, followed by the addition of methyl 5-amino-2-furate (Lancaster) (0.38 g, 2.7 mmol). The reaction mixture was stirred at room temperature for 4 h. Water was added, and the mixture was extracted with dichloromethane twice. The organic layers were combined, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:3) 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 methyl ester as a off white solid (0.1 g, 16%).

Workup

  1. concentrationconcentrated
  2. additionwere added
  3. stirringThe reaction mixture was stirred at room temperature for 4 h
  4. extractionthe mixture was extracted with dichloromethane twice
  5. washwashed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography (EtOAc:hexanes=1:3)

Sources & evidence

ORD record
ord-888ce51edc054607b1f0ec1ca1b11c07
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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