Hydrochloric Acid → HCID 46199554, compound

HRID 1908548Notes

Reaction equation

HRID 1908548 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[C:23]([C:25]([O:27]C)=[O:26])[CH:24]=4)[NH:21][C:20]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.[OH-].[Li+].Cl>O1CCOCC1.O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[C:23]([C:25]([OH:27])=[O:26])[CH:24]=4)[NH:21][C:20]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 59129275HCID 59129275, compound

Product 1

HCID 46199554HCID 46199554, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

Methyl 5-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2-tert-butyl-1H-indole-7-carboxylate (30 mg, 0.069 mmol) was dissolved in a mixture of 1,4-dioxane (1.5 mL) and water (2 mL) containing a magnetic star bar and lithium hydroxide (30 mg, 0.71 mmol). The resulting solution was stirred at 70° C. for 45 minutes. The crude product was then acidified with 2.6 M hydrochloric acid and extracted three times with an equivalent volume of dichloromethane. The dichloromethane extracts were combined, dried over sodium sulfate, filtered, and evaporated to dryness. The residue was dissolved in a minimum of N,N-dimethylformamide and then purified by preparative HPLC using a gradient of 0-99% acetonitrile in water containing 0.05% trifluoroacetic acid to yield 5-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2-tert-butyl-1H-indole-7-carboxylic acid. ESI-MS m/z calc. 434.2. found 435.5. Retention time of 1.85 minutes. 1H NMR (400 MHz, DMSO-d6) δ 13.05 (s, 1H), 9.96 (d, J=1.6 Hz, 1H), 7.89 (d, J=1.9 Hz, 1H), 7.74 (d, J=2.0 Hz, 1H), 7.02 (d, J=1.6 Hz, 1H), 6.96-6.88 (m, 2H), 6.22 (d, J=2.3 Hz, 1H), 6.02 (s, 2H), 1.43-1.40 (m, 2H), 1.37 (s, 9H), 1.06-1.02 (m, 2H).

Workup

  1. additioncontaining a magnetic star bar
  2. extractionextracted three times with an equivalent volume of dichloromethane
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. dissolutionThe residue was dissolved in a minimum of N,N-dimethylformamide
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-baf904125ea24ce8af7fc9a711532a6d
Source dataset
uspto-grants-2013_12
Patent number
US08598181B2

Reaction notes

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