Water → HCID 178489060, compound

HRID 2174139Notes

Reaction equation

HRID 2174139 reaction equation
[C:1]([C:3]1[CH:30]=[CH:29][C:6]2[NH:7][C:8]([C:10]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH2:19][CH2:20][NH:21]4)([CH3:16])[CH2:11][C:12]([O:14]C)=[O:13])=[N:9][C:5]=2[CH:4]=1)#[N:2].O.[Li+].[OH-].[OH-].[Na+]>C1COCC1.CO>[C:1]([C:3]1[CH:30]=[CH:29][C:6]2[NH:7][C:8]([C:10]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][NH:21]4)([CH3:16])[CH2:11][C:12]([OH:14])=[O:13])=[N:9][C:5]=2[CH:4]=1)#[N:2]

Participants

7

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 178500112HCID 178500112, compound

Product 1

HCID 178489060HCID 178489060, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

(±)-Methyl 3-(5-cyano-1H-benzo[d]imidazol-2-yl)-3-(5-methoxy-7-methylindolin-4-yl)butanoate (Example 156-K) (25 mg, 0.062 mmol) was dissolved in THF (0.371 mL), water (0.124 mL) and MeOH (0.124 mL). LiOH (13 mg, 0.304 mmol) was then added and the reaction was stirred for 18 hours at room temperature. At this point, NaOH (1 mL, 2.000 mmol), MeOH (1 mL) and THF (3 mL) were added and the reaction was stirred for further 4 hours. The reaction was then concentrated and diluted with EtOAc and water. The layers were separated, the aqueous layer was adjusted to pH=1 and directly purified using RP-HPLC (HC-A) to isolate the title compound. 1H NMR (TFA salt, 400 MHz, DMSO-d6) δ ppm 11.01 (br. s., 1H) 8.11 (br. s., 1H) 7.68 (q, J=7.66 Hz, 2H) 7.22 (br. s., 1H) 6.74 (s, 1H) 5.95 (br. s., 1H) 3.55 (d, J=15.16 Hz, 1H) 3.43 (s, 1H) 3.39 (s, 3H) 2.44 (s, 3H) 1.99-2.15 (m, 3H). HRMS calcd. for C22H20N4O3 (M+H)+ 389.1614. found 389.1609.

Workup

  1. stirringthe reaction was stirred for further 4 hours
  2. concentrationThe reaction was then concentrated
  3. additiondiluted with EtOAc and water
  4. customThe layers were separated
  5. customdirectly purified

Sources & evidence

ORD record
ord-07a34dd7e968493ab9a82f95292a274f
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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