Citric Acid → HCID 86673870, compound

HRID 1527542Notes

Reaction equation

HRID 1527542 reaction equation
[F:1][C:2]([F:31])([F:30])[O:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]([C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[C:18](=[O:29])[CH2:19][C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[NH:22][CH:21]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1.[C:32](Cl)(=[O:34])[CH3:33].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.CN(C1C=CN=CC=1)C>[F:31][C:2]([F:1])([F:30])[O:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]([C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[C:18](=[O:29])[CH2:19][C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]([C:32](=[O:34])[CH3:33])[CH:21]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 311Citric AcidHCID 6367Acetyl chlorideHCID 86673871HCID 86673871, compound

Product 1

HCID 86673870HCID 86673870, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-1-(2-1H-indol-3-yl-acetyl)-pyrrolidine-2-carboxylic acid (3-trifluoromethoxy-phenyl)-amide (100 mg, 0.232 mmol) in DMF (1.5 mL) under nitrogen atmosphere were added acetyl chloride (148 μl, 2.09 mmol) followed by DMAP (85 mg, 0.7 mmol) and the reaction mixture was heated at 80° C. for 18 h. After completion of the reaction, the mixture was poured into citric acid (10% solution), and extracted three times with EtOAc. The combined organic layers were washed twice with water, dried over Na2SO4, filtered and concentrated. The crude material was purified by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 20% CH3CN/H2O 2.5 min, 20-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min) to give after lyophilization of the purified fractions the desired compound.

Workup

  1. customAfter completion of the reaction
  2. extractionextracted three times with EtOAc
  3. washThe combined organic layers were washed twice with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 20% CH3CN/H2O 2.5 min, 20-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min)
  8. customto give after lyophilization of the
  9. custompurified fractions the desired compound

Sources & evidence

ORD record
ord-2f7f87f9fa8646b79a3c9c79aa622574
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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