Water → HCID 86686854, compound

HRID 402957Notes

Reaction equation

HRID 402957 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[O:26])=[CH:21][N:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:33]1[N:42]=[CH:41][C:40]2[C:35](=[C:36]([F:47])[CH:37]=[C:38]([C:43]([CH3:46])([CH3:45])[CH3:44])[CH:39]=2)[C:34]1=[O:48])(=O)C.[OH-].[Na+].C(OCC)(=O)C.O>O1CCOCC1>[C:43]([C:38]1[CH:39]=[C:40]2[C:35](=[C:36]([F:47])[CH:37]=1)[C:34](=[O:48])[N:33]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:24]=[CH:23][C:22]([C:25]([N:27]5[CH2:28][CH2:29][O:30][CH2:31][CH2:32]5)=[O:26])=[CH:21][N:20]=4)[N:15]=[CH:14][N:13]=3)[C:6]=1[CH2:5][OH:4])[N:42]=[CH:41]2)([CH3:46])([CH3:44])[CH3:45]

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 866868532-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(6-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)pyrimidin-4-yl)benzyl acetate

Product 1

HCID 86686854HCID 86686854, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(6-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)pyrimidin-4-yl)benzyl acetate (90 mg, 0.14 mmol) in 1,4-dioxane (5 mL) was added 1N NaOH (10 mL). The mixture was stirred at room temperature for 2 hrs. The mixture was acidified to pH=2, followed by addition of ethyl acetate (50 mL) and H2O (20 mL). The organic phase was washed with H2O (2×20 mL), then brine (2×20 mL) and dried over Na2SO4. After filtration and concentration, the residue was purified by prep-HPLC to afford 6-tert-butyl-8-fluoro-2-(2-(hydroxymethyl)-3-(6-(5-(morpholine-4-carbonyl)pyridin-2-ylamino)pyrimidin-4-yl)phenyl)-phthalazin-1(2H)-one (30 mg, 36%). 1H NMR (300 MHz, CD3OD): δ 8.98 (s, 1H), 8.52-8.48 (m, 2H), 8.39 (s, 1H), 7.99-7.95 (m, 1H), 7.85 (s, 1H), 7.73-7.68 (m, 5H), 4.55 (s, 2H), 3.72 (brs, 8H), 1.46 (s, 9H). LC-MS (ESI): 610.3, [M+1]+ HPLC: 97.17% at 214 nm, 99.01% at 254 nm, tR=5.761 min.

Workup

  1. washThe organic phase was washed with H2O (2×20 mL)
  2. dry with materialbrine (2×20 mL) and dried over Na2SO4
  3. filtrationAfter filtration and concentration
  4. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-282afe7d4c80427a8d40327de34f7e2a
Source dataset
uspto-grants-2014_06
Patent number
US08742098B2

Reaction notes

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