Sodium Hydroxide → HCID 56656504, compound

HRID 1431047Notes

Reaction equation

HRID 1431047 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[CH2:45][CH:44]([O:46][CH3:47])[CH2:43]5)=[CH:37][N:36]=4)[C:31](=[O:48])[N:30]([CH3:49])[N:29]=3)[C:18]=1[CH2:19][O:20]C(=O)C)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C1COCC1.O.C(OCC)(=O)C>[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[CH2:45][CH:44]([O:46][CH3:47])[CH2:43]5)=[CH:37][N:36]=4)[C:31](=[O:48])[N:30]([CH3:49])[N:29]=3)[C:18]=1[CH2:19][OH:20])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 66742743HCID 66742743, compound

Product 1

HCID 56656504HCID 56656504, compoundYield 46.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{5-[5-(3-methoxy-azetidin-1-ylmethyl)-pyridin-2-ylamino]-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl}-benzyl ester (175 mg, 0.26 mmol, Eq: 1.0) was dissolved in 2.6 ml of THF. Sodium hydroxide (1.3 ml of a 1.0M solution in water, 1.3 mmol, Eq: 5.0) was added dropwise. The reaction was stirred at room temperature overnight. Starting material was still present the next morning. The reaction was heated at 50° C. for two hours at which point no starting material remained. The reaction was diluted with ethyl acetate and water and the layers were separated. The organic layer was dried and concentrated. The residue was triturated with isopropyl acetate, filtered, washed with ether, and dried in a vacuum oven to give 75 mg (45.7%) of the desired product as a white powder. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.37 (s, 9H) 2.79 (t, J=6.80 Hz, 2H) 3.11 (s, 3H) 3.37-3.44 (m, 2H) 3.46 (s, 2H) 3.77 (s, 3H) 3.92 (t, J=5.85 Hz, 1H) 4.40 (br.s., 2H) 4.52-4.63 (m, 1H) 7.40-7.62 (m, 5H) 7.74 (d, J=13.22 Hz, 1H) 7.86 (s, 1H) 8.15 (s, 1H) 8.48-8.55 (m, 2H) 9.36-9.44 (m, 1H). MS: (M+H)+=626. MP=140-142° C.

Workup

  1. temperatureThe reaction was heated at 50° C. for two hours at which point no starting material
  2. customthe layers were separated
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customThe residue was triturated with isopropyl acetate
  6. filtrationfiltered
  7. washwashed with ether
  8. customdried in a vacuum oven

Sources & evidence

ORD record
ord-cfbdfdb1eef1418a9621d3bf86bad579
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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