Ethanol → 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrazole-3-carboxylic acid amide

HRID 1025612Notes

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:18]([CH2:30][OH:31])=[C:19]([N:23]3[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C([OH:34])C.O>C(Cl)Cl>[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:18]([CH2:30][OH:31])=[C:19]([N:23]3[CH:27]=[CH:26][C:25]([C:28]([NH2:29])=[O:34])=[N:24]3)[CH:20]=[CH:21][CH:22]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 80 °C

Procedure

In a 10 mL round-bottomed flask, 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-pyrazole-3-carbonitrile (16 mg, 38.3 μmol, Eq: 1.00) and [hydrogen bis(dimethylphosphinito-kP)]platinum (II) (1 mg, 2.33 μmol, Eq: 0.0608) were combined with ethanol (821 μl) and water (410 μl) to give a colorless solution. The reaction mixture was heated to 80° C. and stirred for 2 h. The reaction mixture was diluted with DCM. The reaction mixture was filtered through glass fiber paper. The crude material was purified by preparative HPLC to give 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1H-pyrazole-3-carboxylic acid amide (11 mg, 66%, [M+H]+ 436) of lyophilized white solid.

Workup

customto give a colorless solution
filtrationThe reaction mixture was filtered through glass fiber paper
customThe crude material was purified by preparative HPLC

Sources & evidence

ORD record: ord-f5620f88fadc4ae392f48fe3c610cbcf
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729078B2

Reaction notes

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