Sodium Hydroxide → HCID 86698782, compound

HRID 338450Notes

Reaction equation

HRID 338450 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:18]([O:20]C)=[O:19])=[CH:7][N:8]2C(OC(C)(C)C)=O)=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)=[CH:24][CH:23]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:18]([OH:20])=[O:19])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:22]1[CH:23]=[CH:24][C:25]([O:28][CH2:29][C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86698781HCID 86698781, compound

Product 1

HCID 86698782HCID 86698782, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of crude 1-tert-butyl 3-methyl 6-chloro-5-[4-(pyridin-3-ylmethoxy)phenyl]-1H-indole-1,3-dicarboxylate (37 mg, 0.075 mmol), methanol (0.8 mL) and 1M aqueous sodium hydroxide (0.45 mL, 0.45 mmol) was sealed in a vial and heated at 75° C. for 17 hours, causing a solution to form. After cooling to room temperature, the reaction mixture was concentrated via a stream of nitrogen, and diluted with ethyl acetate and saturated aqueous citric acid slowly. The layers were separated, and the aqueous layer was extracted two times with ethyl acetate. The organic layers were combined, concentrated in vacuo, and the resulting clear oil was dissolved in DMSO (0.9 mL) and purified via reverse phase prep-HPLC to give the title compound (6.4 mg, 23% over two steps). MS (ES+) 379.1 (M+H)+. Retention time: 2.28 min. Column: Waters Atlantis dC18 4.6×50 mm, 5 μm. Modifier: TFA 0.05%. Gradient: 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. Flow: 2.0 mL/min.

Workup

  1. customwas sealed in a vial and
  2. customto form
  3. temperatureAfter cooling to room temperature
  4. concentrationthe reaction mixture was concentrated via a stream of nitrogen
  5. additiondiluted with ethyl acetate and saturated aqueous citric acid slowly
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted two times with ethyl acetate
  8. concentrationconcentrated in vacuo
  9. dissolutionthe resulting clear oil was dissolved in DMSO (0.9 mL)
  10. custompurified via reverse phase prep-HPLC

Sources & evidence

ORD record
ord-e90140b0d548427e9a2d447be6323e83
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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