Lithium Hydroxide → N-[2-[[6-[[5-[2-(6-tert-butyl-8-fluoro-1-oxo-phthalazin-2-yl)-3-(hydroxymethyl)-4-pyridyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]oxy]ethyl]prop-2-enamide

HRID 1774635Notes

Reaction equation

HRID 1774635 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:35]2[N:44]=[CH:43][C:42]3[C:37](=[C:38]([F:49])[CH:39]=[C:40]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH:41]=3)[C:36]2=[O:50])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH2:26][CH2:27][NH:28][C:29](=[O:32])[CH:30]=[CH2:31])[N:20]=2)[C:15](=[O:33])[N:14]([CH3:34])[CH:13]=1)(=O)C.[Li+].[OH-]>C1COCC1.CC(O)C.O>[C:45]([C:40]1[CH:41]=[C:42]2[C:37](=[C:38]([F:49])[CH:39]=1)[C:36](=[O:50])[N:35]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[N:20]=[C:21]([O:25][CH2:26][CH2:27][NH:28][C:29](=[O:32])[CH:30]=[CH2:31])[CH:22]=[CH:23][CH:24]=4)[C:15](=[O:33])[N:14]([CH3:34])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:44]=[CH:43]2)([CH3:48])([CH3:47])[CH3:46]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118116891(4-(5-(6-(2-acrylamidoethoxyl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)pyridin-3-yl)methyl acetate

Product 1

HCID 118116889N-[2-[[6-[[5-[2-(6-tert-butyl-8-fluoro-1-oxo-phthalazin-2-yl)-3-(hydroxymethyl)-4-pyridyl]-1-methyl-2-oxo-3-pyridyl]amino]-2-pyridyl]oxy]ethyl]prop-2-enamideYield 10%

Reagents, catalysts & solvents 1

HCID 22722550Tetrahydrofuran water isopropanolSolvent

Procedure

A mixture of 104d (140 mg, 0.21 mmol) and LiOH (44 mg, 1.05 mmol) in THF/i-PrOH/water (2.0 mL/1.2 mL/0.8 mL) was stirred at rt for 1 h. The mixture was extracted with EA. The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by prep-HPLC to give 104 (10 mg, 10% for two steps) as a light yellow solid. 1H NMR (500 MHz, CDCl3): δ 8.72-8.66 (m, 2H), 8.33 (s, 1H), 7.91 (s, 1H), 7.59-7.47 (m, 6H), 6.51 (s, 1H), 6.44 (d, J=10.0 Hz, 1H), 6.24-6.16 (m, 2H), 5.99-5.94 (m, 1H), 5.50 (d, J=10.0 Hz, 1H), 4.58-4.48 (m, 2H), 4.28-4.21 (m, 2H), 3.99-3.57 (m, 5H), 1.43 (s, 9H). MS-ESI: [M+H]+ 640.3

Workup

  1. extractionThe mixture was extracted with EA
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-85bdc4895cda4825a7843b5b517512ca
Source dataset
uspto-grants-2016_02
Patent number
US09260415B2

Reaction notes

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