Water → 6-tert-Butyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2H-phthalazin-1-one

HRID 449654Notes

Reaction equation

HRID 449654 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[CH:33]=[C:32]([NH:34][C:35]4[CH:40]=[CH:39][C:38]([CH2:41][N:42]5[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]5)=[CH:37][N:36]=4)[C:31](=[O:49])[N:30]([CH3:50])[N:29]=3)[C:18]=1[CH2:19][O:20]C(=O)C)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].O>CO>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]3[CH:33]=[C:32]([NH:34][C:35]4[CH:40]=[CH:39][C:38]([CH2:41][N:42]5[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]5)=[CH:37][N:36]=4)[C:31](=[O:49])[N:30]([CH3:50])[N:29]=3)[C:18]=1[CH2:19][OH:20])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 66743194Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{1-methyl-5-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-benzyl ester

Product 1

HCID 566559776-tert-Butyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-phenyl)-2H-phthalazin-1-oneYield 86.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{1-methyl-5-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridazin-3-yl}-benzyl ester (4.5 g, 6.61 mmol, Eq: 1.00) and potassium carbonate (1.37 g, 9.92 mmol, Eq: 1.50) were dissolved in methanol and heated at 40° C. for 1 hour. The reaction was cooled to room temperature and water was added dropwise. The reaction was stirred at room temperature overnight. The solid that formed was filtered, washed with water, and dried in a vacuum oven over the weekend to give 3.64 g (86.2%) of an off-white crystalline solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.39 (s, 1H) 8.53 (s, 1H) 8.50 (d, J=2.3 Hz, 1H) 8.15 (d, J=1.9 Hz, 1H) 7.86 (d, J=1.5 Hz, 1H) 7.74 (dd, J=13.4, 1.7 Hz, 1H) 7.57-7.62 (m, 1H) 7.50-7.57 (m, 2H) 7.43-7.49 (m, 2H) 4.52-4.61 (m, 1H) 4.40 (br. s., 2H) 3.77 (s, 3H) 3.36 (s, 2H) 2.30 (br. s., 8H) 2.11 (s, 3H) 1.37 (s, 9H). MS: (M+H)+=639.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customThe solid that formed
  3. filtrationwas filtered
  4. washwashed with water
  5. customdried in a vacuum oven over the weekend

Sources & evidence

ORD record
ord-34ab298025a94110b0f0ed80d3276f8b
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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