6-tert-butyl-2-(4-(5-(diphenylmethyleneamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-(hydroxymethyl)pyridin-2-yl)-8-fluorophthalazin-1(2H)-one → 2-(4-(5-amino-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-(hydroxymethyl)-pyridin-2-yl)-6-tert-butyl-8-fluorophthalazin-1(2H)-one

HRID 520300Notes

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[C:22]([CH2:23][OH:24])=[C:21]([C:25]3[CH:30]=[C:29]([N:31]=C(C4C=CC=CC=4)C4C=CC=CC=4)[C:28](=[O:45])[N:27]([CH3:46])[CH:26]=3)[CH:20]=[CH:19][N:18]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2]>Cl.O1CCOCC1>[NH2:31][C:29]1[C:28](=[O:45])[N:27]([CH3:46])[CH:26]=[C:25]([C:21]2[CH:20]=[CH:19][N:18]=[C:17]([N:10]3[N:9]=[CH:8][C:7]4[C:12](=[C:13]([F:15])[CH:14]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=4)[C:11]3=[O:16])[C:22]=2[CH2:23][OH:24])[CH:30]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of 123b (1.6 g, 2.6 mmol) in HCl/dioxane (4M, 10 mL) was stirred at 25° C. for 1 h. The mixture was evaporated in vacuo and the residue was purified by reverse-phase prep-HPLC to afford 123d (580 mg, 50%) as a pale yellow solid. MS-ESI: [M+H]+ 450.1. 1H NMR (500 MHz, DMSO-d6) δ 8.53-8.52 (m, 2H), 7.90 (d, J=1.0 Hz, 1H), 7.79-7.76 (m, 1H), 7.45 (d, J=5.0 Hz, 1H), 7.24 (d, J=2.5 Hz, 1H), 6.65 (d, J=2.0 Hz, 1H), 5.33 (s, 2H), 4.95-4.93 (m, 1H), 4.39 (s, 2H), 3.52 (s, 3H), 1.38 (s, 9H).

Workup

customThe mixture was evaporated in vacuo
customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record: ord-3ec2ce516a63490da055b73ea1fafd8b
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09326985B2

Reaction notes

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