Lithium Hydroxide → 6-tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(4-methyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-one

HRID 407790Notes

Reaction equation

HRID 407790 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:31]2[N:40]=[CH:39][C:38]3[C:33](=[C:34]([F:45])[CH:35]=[C:36]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH:37]=3)[C:32]2=[O:46])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:28]=[C:22]3[CH:23]([CH3:27])[O:24][CH2:25][CH2:26][N:21]3[N:20]=2)[C:15](=[O:29])[N:14]([CH3:30])[CH:13]=1)(=O)C.[OH-].[Li+].C(O)(C)C.C1COCC1>O>[C:41]([C:36]1[CH:37]=[C:38]2[C:33](=[C:34]([F:45])[CH:35]=1)[C:32](=[O:46])[N:31]([C:7]1[C:6]([CH2:5][OH:4])=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[CH:28]=[C:22]5[CH:23]([CH3:27])[O:24][CH2:25][CH2:26][N:21]5[N:20]=4)[C:15](=[O:29])[N:14]([CH3:30])[CH:13]=3)[CH:10]=[CH:9][N:8]=1)[N:40]=[CH:39]2)([CH3:42])([CH3:43])[CH3:44]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 22597222Tetrahydrofuran 2-propanolHCID 86684051(2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-(1-methyl-5-(4-methyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)pyridin-3-yl)methyl acetate

Product 1

HCID 866840536-tert-butyl-8-fluoro-2-[3-(hydroxymethyl)-4-[1-methyl-5-[(4-methyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl)amino]-6-oxo-3-pyridyl]-2-pyridyl]phthalazin-1-oneYield 15.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 25-mL round-bottomed flask equipped with a magnetic stirrer was charged with 150i (48 mg, 1.0 eq., 0.077 mmol), lithium hydroxide (9.2 mg, 5.0 eq., 0.38 mmol), i-propanol/THF (4/4 mL), and water (1 mL). The mixture was stirred at room temperature for 1 h and concentrated under reduced pressure. The residue was purified by reverse-phase prep-HPLC to afford 150 as a yellow solid (6.8 mg, 15%). MS-ESI: [M+H]+ 585.8. 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J=4.5 Hz, 1H), 8.35 (d, J=2.0 Hz, 1H), 8.03 (d, J=1.5 Hz, 1H), 7.59-7.53 (m, 4H), 7.47 (s, 1H), 5.72 (s, 1H), 4.82-4.78 (m, 1H), 4.52-4.49 (m, 2H), 4.33-4.30 (m, 1H), 4.30-4.27 (m, 1H), 4.02-3.98 (m, 3H), 3.73 (s, 3H), 1.54 (d, J=7.0 Hz, 3H), 1.48 (s, 9H).

Workup

  1. customA 25-mL round-bottomed flask equipped with a magnetic stirrer
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-37c4d10aa94e4c5e9bb11a6c59366189
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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