Methyl iodide → HCID 68284557, compound

HRID 1527569Notes

Reaction equation

HRID 1527569 reaction equation
[Cl:1][C:2]1[C:3]([F:34])=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][NH:6][C:7]([C@@H:9]1[CH2:13][C@@H:12]([F:14])[CH2:11][N:10]1[C:15](=[O:30])[CH2:16][N:17]1[C:25]2[C:20](=[CH:21][C:22]([OH:26])=[CH:23][CH:24]=2)[C:19]([C:27](=[O:29])[CH3:28])=[CH:18]1)=[O:8].[OH-].[K+].I[CH3:38]>CS(C)=O>[Cl:1][C:2]1[C:3]([F:34])=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][NH:6][C:7]([C@@H:9]1[CH2:13][C@@H:12]([F:14])[CH2:11][N:10]1[C:15](=[O:30])[CH2:16][N:17]1[C:25]2[C:20](=[CH:21][C:22]([O:26][CH3:38])=[CH:23][CH:24]=2)[C:19]([C:27](=[O:29])[CH3:28])=[CH:18]1)=[O:8]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 68284042HCID 68284042, compound

Product 1

HCID 68284557HCID 68284557, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of (2S,4R)-1-[2-(3-acetyl-5-hydroxy-indol-1-yl)-acetyl]-4-fluoro-pyrrolidine-2-carboxylic acid 3-chloro-2-fluoro-benzylamide Example 579 (28.0 mg, 0.057 mmol) in DMSO (2 mL) was treated with potassium hydroxide (15.0 mg, 0.257 mmol). The mixture was stirred at RT for 5 min, followed by addition of iodomethane (0.006 mL, 0.089 mmol) and stirring at RT for 60 h. The reaction mixture was partitioned between water and CH2Cl2 and the aqueous layer was extracted with CH2Cl2 (2×). The combined organics were washed with brine (3×), dried (phase separator) and concentrated under reduced pressure. The crude product was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 19×50 mm, flow: 20 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA) to afford after lyophilization of the purified fractions the title compound as a solid. MS (LC/MS): 504 [M+H]+, 526 [M+Na]+; tR (HPLC conditions k): 3.38 min.

Workup

  1. stirringstirring at RT for 60 h
  2. customThe reaction mixture was partitioned between water and CH2Cl2
  3. extractionthe aqueous layer was extracted with CH2Cl2 (2×)
  4. washThe combined organics were washed with brine (3×)
  5. customdried (phase separator)
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 19×50 mm, flow: 20 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-fe1bb6300d9746e5b08bf465addd0669
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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