Ammonia methanol → 2-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-4-methyl-oxazole-5-carboxylic acid amide

HRID 1025575Notes

Reaction equation

HRID 1025575 reaction equation
C([O:3][C:4]([C:6]1[O:10][C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N:17]3[N:26]=[CH:25][C:24]4[C:19](=[CH:20][CH:21]=[C:22]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:23]=4)[C:18]3=[O:31])[C:12]=2[CH2:32][O:33]C(=O)C)=[N:8][C:7]=1[CH3:37])=O)C.[NH3:38].CO>>[C:27]([C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[C:18](=[O:31])[N:17]([C:13]1[C:12]([CH2:32][OH:33])=[C:11]([C:9]3[O:10][C:6]([C:4]([NH2:38])=[O:3])=[C:7]([CH3:37])[N:8]=3)[CH:16]=[CH:15][CH:14]=1)[N:26]=[CH:25]2)([CH3:29])([CH3:28])[CH3:30]

Participants

3

Reactant 2

HCID 21705897Ammonia methanolHCID 710084822-[2-acetoxymethyl-3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-phenyl]-4-methyl-oxazole-5-carboxylic acid ethyl ester

Product 1

HCID 710083772-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-4-methyl-oxazole-5-carboxylic acid amideYield 68%

Procedure

The above 2-[2-acetoxymethyl-3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-phenyl]-4-methyl-oxazole-5-carboxylic acid ethyl ester was dissolved in 10 mL of NH3/MeOH. The reaction was stirred at room temperature for two days. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography (petroleum ether/ethyl acetate=1:1) to give 2-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-4-methyl-oxazole-5-carboxylic acid amide (47 mg, yield 68% for two steps) as a white solid. 1H NMR (300 MHz, DMSO-d6): δ 8.57 (s, 1H), 8.24 (d, J=8.1 Hz, 1H), 8.20 (dd, J=2.1, 8.4 Hz, 1H), 8.06-8.00 (m, 2H), 7.66-7.58 (m, 2H), 4.73-4.57 (m, 2H), 2.46 (s, 3H), 1.41 (s, 9H). LC-MS calcd for C24H24N4O4 (m/e) 432.18, obsd 433 [M+H]+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was purified by silica gel chromatography (petroleum ether/ethyl acetate=1:1)

Sources & evidence

ORD record
ord-1715dc9d65ed4e9686ced71776f7de46
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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