Sodium Hydroxide → HCID 178489064, compound

HRID 2174109Notes

Reaction equation

HRID 2174109 reaction equation
[C:1]([C:3]1[CH:29]=[CH:28][C:6]2[NH:7][C:8]([CH:10]([C:16]3[C:24]([O:25][CH3:26])=[CH:23][C:22]([CH3:27])=[C:21]4[C:17]=3[CH:18]=[CH:19][NH:20]4)[CH2:11][C:12]([O:14]C)=[O:13])=[N:9][C:5]=2[CH:4]=1)#[N:2].[OH-].[Na+]>CO.O>[C:1]([C:3]1[CH:29]=[CH:28][C:6]2[NH:7][C:8]([CH:10]([C:16]3[C:24]([O:25][CH3:26])=[CH:23][C:22]([CH3:27])=[C:21]4[C:17]=3[CH:18]=[CH:19][NH:20]4)[CH2:11][C:12]([OH:14])=[O:13])=[N:9][C:5]=2[CH:4]=1)#[N:2]

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide3×HCID 178500072HCID 178500072, compound

Product 1

HCID 178489064HCID 178489064, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of (±)-methyl 3-(5-cyano-1H-benzo[d]imidazol-2-yl)-3-(5-methoxy-7-methyl-1H-indol-4-yl)propanoate (Example 145-C) (254 mg, 0.248 mmol) in MeOH (6 mL) was added 1N NaOH (1.439 mL, 1.439 mmol) and the resulting solution was stirred at rt. After stirring for 1.5 hrs additional 1N NaOH (1.439 mL, 1.439 mmol) was added to the mixture and the mixture was stirred at rt for 16 hrs. At this point, additional 1N NaOH (1.439 mL, 1.439 mmol) was added and the mixture was heated to 60° C. for 3.5 hrs. The reaction mixture was then cooled to rt, diluted with water and the aqueous layer (pH=10) was washed AcOEt (4×). The water layer was acidified with 1N HCl (pH=2-3) and then extracted with AcOEt. The organic layer was washed with water (2×). The combined organic layers were passed through a phase separator and concentrated to give crude product that was purified via preparative HPLC (HC-B) to obtain the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.50-12.64 (m, 1H) 10.92 (br. s., 1H) 7.87-8.25 (m) 7.48 (d) 7.13 (t, J=2.78 Hz, 1H) 6.79 (s, 1H) 5.97 (dd, J=2.91, 1.89 Hz, 1H) 5.34 (dd, J=9.73, 4.67 Hz, 1H) 3.78 (s, 3H) 3.54-3.69 (m, 1H) 2.59-2.65 (m, 1H) 2.44 (s, 3H). HRMS calcd. for C21H18N4O3 (M+H)+ 375.1457. found 375.1458.

Workup

  1. additionwas added to the mixture
  2. stirringthe mixture was stirred at rt for 16 hrs
  3. temperaturethe mixture was heated to 60° C. for 3.5 hrs
  4. temperatureThe reaction mixture was then cooled to rt
  5. washthe aqueous layer (pH=10) was washed AcOEt (4×)
  6. extractionextracted with AcOEt
  7. washThe organic layer was washed with water (2×)
  8. concentrationconcentrated
  9. customto give crude product that
  10. customwas purified via preparative HPLC (HC-B)

Sources & evidence

ORD record
ord-aecbc46d4b304a41a5ce0c22406b6b72
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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