Lithium Hydroxide → 6-Tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methylisothiazol-3-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-one

HRID 407816Notes

Reaction equation

HRID 407816 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:27]2[N:36]=[CH:35][C:34]3[C:29](=[C:30]([F:41])[CH:31]=[C:32]([C:37]([CH3:40])([CH3:39])[CH3:38])[CH:33]=3)[C:28]2=[O:42])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[S:21][N:20]=2)[C:15](=[O:25])[N:14]([CH3:26])[CH:13]=1)(=O)C.[OH-].[Li+]>C1COCC1.C(O)(C)C.O>[C:37]([C:32]1[CH:33]=[C:34]2[C:29](=[C:30]([F:41])[CH:31]=1)[C:28](=[O:42])[N:27]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:23]=[C:22]([CH3:24])[S:21][N:20]=4)[C:15](=[O:25])[N:14]([CH3:26])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:36]=[CH:35]2)([CH3:40])([CH3:38])[CH3:39]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 86684073(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(5-methylisothiazol-3-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl Acetate

Product 1

HCID 866840766-Tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(5-methylisothiazol-3-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-oneYield 50%

Reagents, catalysts & solvents 1

HCID 22722550Tetrahydrofuran water isopropanolSolvent

Procedure

To a solution of 157a (60 mg, 0.10 mmol) in THF/i-propanol/water (4 mL/4 mL/1 mL) was added lithium hydroxide (24 mg, 1.0 mmol). The reaction mixture was stirred at room temperature for 0.5 h and concentrated under reduced pressure. The residue was diluted with water (10 mL) and extracted with ethyl acetate (3×15 mL). The combined organic layer was dried with Na2SO4 and concentrated to afford a yellow solid, which was purified by reverse-phase prep-HPLC to afford 157 as a yellow solid (27 mg, 50%). MS-ESI: [M+H]+ 546.7. 1H NMR (500 MHz, DMSO-d6) δ 9.28 (s, 1H), 8.60-8.54 (m, 3H), 7.90 (s, 1H), 7.78 (d, J=16.0 Hz, 1H), 7.55-7.50 (m, 2H), 7.04 (s, 1H), 4.89 (t, J=6.5 Hz, 1H), 4.43-4.41 (m, 2H), 3.61 (s, 3H), 2.48 (s, 3H), 1.40 (s, 9H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with water (10 mL)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. dry with materialThe combined organic layer was dried with Na2SO4
  5. concentrationconcentrated
  6. customto afford a yellow solid, which
  7. customwas purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-efde74ed110a4fad9af9b75a05e6c63f
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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