2-Methyl-2-butene → 6-chloro-5-[4-(1-methylpyrrolidin-2-yl)phenyl]-1H-indole-3-carboxylic acid

HRID 338432Notes

Reaction equation

HRID 338432 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:23][CH2:22][CH2:21][N:20]2[CH3:24])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:31].[Na+].P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].S([O-])([O-])=O.[Na+].[Na+]>C(#N)C.C(O)(C)(C)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:31])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]([CH:19]2[CH2:23][CH2:22][CH2:21][N:20]2[CH3:24])=[CH:17][CH:18]=1

Participants

8

Reactant 5

HCID 105532-Methyl-2-buteneHCID 24243Trisodium PhosphateHCID 24437Sodium SulfiteHCID 23668197Sodium ChloriteHCID 866987636-chloro-5-[4-(1-methylpyrrolidin-2-yl)phenyl]-1H-indole-3-carbaldehyde

Product 1

HCID 866987646-chloro-5-[4-(1-methylpyrrolidin-2-yl)phenyl]-1H-indole-3-carboxylic acidYield 6.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 22050040Acetonitrile tert-butanolSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 6-chloro-5-[4-(1-methylpyrrolidin-2-yl)phenyl]-1H-indole-3-carbaldehyde (150 mg, 0.443 mmol) in acetonitrile/t-butanol (9 mL/9 mL) was added 2-methyl-2-butene (7.50 mL, 28.2 mmol). The reaction mixture was cooled to 0° C. followed by the addition of an aqueous solution of sodium chlorite (598 mg, 8.86 mmol) and sodium phosphate (monobasic and monohydrate, 1220 mg, 8.860 mmol) in water (9 mL) dropwise via syringe. The ice bath was removed and the reaction was stirred at room temperature overnight. The reaction was quenched with sodium sulfite (1.12 g, 8.86 mmol) in water (3 mL). The reaction mixture was concentrated under reduced pressure to remove the volatile organics. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by reverse phase HPLC to give the title compound (10 mg, 5.0% yield). MS (ES+) 355.0 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.11 (s, 1H), 7.97 (s, 1H), 7.59-7.58 (m, 5H), 4.19 (m, 1H), 3.74-3.71 (m, 1H), 3.17-3.14 (m, 1H), 2.70 (s, 3H), 2.55-2.52 (m, 1H), 2.33-2.21 (m, 1H), 2.28-2.21 (m, 3H).

Workup

  1. customThe ice bath was removed
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customto remove the volatile organics
  4. extractionThe aqueous layer was extracted three times with ethyl acetate
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-1810c10be1fd4b73bb225eb662e627e5
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

Loading…