Sodium Hydroxide → 4-[3-(6-tert-Butyl-3-methyl-1-oxo-3,4-dihydro-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid amide

HRID 1025580Notes

Reaction equation

HRID 1025580 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:16]=[C:15]([C:17](=[O:19])[NH2:18])[N:14]([CH3:20])[CH:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:21]1[N:30]([CH3:31])[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:27]=2)[C:22]1=[O:36])(=O)C.[OH-].[Na+]>O1CCCC1.C([O-])(O)=O.[Na+].ClCCl>[C:32]([C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][CH:25]=1)[C:22](=[O:36])[N:21]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:16]=[C:15]([C:17]([NH2:18])=[O:19])[N:14]([CH3:20])[CH:13]=3)[CH:10]=[CH:9][CH:8]=1)[N:30]([CH3:31])[CH2:29]2)([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 710081532-(6-tert-butyl-3-methyl-1-oxo-3,4-dihydrophthalazin-2(1H)-yl)-6-(5-carbamoyl-1-methyl-1H-pyrrol-3-yl)benzyl acetate

Product 1

HCID 710086164-[3-(6-tert-Butyl-3-methyl-1-oxo-3,4-dihydro-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid amideYield 99%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

To 2-(6-tert-butyl-3-methyl-1-oxo-3,4-dihydrophthalazin-2(1H)-yl)-6-(5-carbamoyl-1-methyl-1H-pyrrol-3-yl)benzyl acetate (31 mg, 63.4 μmol, Eq: 1.00) in tetrahydrofuran was added NaOH (1.0 M (aqueous) 1.0 mL, 1.00 mmol, Eq: 15.8). The reaction mixture heated at 60° C. for 4 h. The mixture was cooled to room temperature. The solution was diluted with sat NaHCO3 (aqueous) and dichloromethane. The layers were separated. The aqueous layer was extracted once with dichloromethane. The organic extracts were combined and dried over MgSO4. The solution was filtered. Concentrated in vacuo to give 4-[3-(6-tert-Butyl-3-methyl-1-oxo-3,4-dihydro-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid amide (28 mg, 99%): 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.26-1.40 (m, 9H) 2.56 (s, 3H) 3.95 (s, 3H) 4.53 (br. s., 2H) 5.23 (s, 2H) 6.93 (d, J=1.89 Hz, 1H) 7.14 (d, J=1.89 Hz, 1H) 7.24-7.38 (m, 3H) 7.39-7.53 (m, 1H) 7.64 (dd, J=5.67, 3.40 Hz, 1H) 8.01 (d, J=8.31 Hz, 1H). LC/MS-ESI observed [M+H]+ 447.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customThe layers were separated
  3. extractionThe aqueous layer was extracted once with dichloromethane
  4. dry with materialdried over MgSO4
  5. filtrationThe solution was filtered
  6. concentrationConcentrated in vacuo

Sources & evidence

ORD record
ord-608079c0574c45b88ec52367b57c731a
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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