7,12-Dimethylbenz(a)anthracene → 6-(3-amino-2-fluoropropyl)-9-chloro[1,2,4]triazolo[3,4-a]isoquinolin-3(2H)-one

HRID 1783763

Reaction equation

C([NH:4][CH2:5][CH:6]([F:23])[CH2:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([Cl:18])=[CH:15][CH:16]=2)[C:11]2=[N:19][NH:20][C:21](=[O:22])[N:10]2[CH:9]=1)C=C.CC1C2C(=CC=CC=2)C(C)=C2C=1C=CC1C2=CC=CC=1>C(Cl)CCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:4][CH2:5][CH:6]([F:23])[CH2:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([Cl:18])=[CH:15][CH:16]=2)[C:11]2=[N:19][NH:20][C:21](=[O:22])[N:10]2[CH:9]=1

Participants

Conditions

Temperature: 50 °C

Procedure

6-[3-(allylamino)-2-fluoropropyl]-9-chloro[1,2,4]triazolo[3,4-a]isoquinolin-3(2H)-one (6-4)(18 mg, 0.054 mmol, 1.0 equiv) and DMBA (25.2 mg, 0.16 mmol, 3.0equiv) and tetrakis(triphenylphosphine)palladium(0) (3 mg, 2.60 μmol, 0.05 equiv) were suspended in ClCH2CH2Cl (1 mL). The resulted yellow suspension was heated at 50° C. LCMS at 5 hours showed mostly product. The crude was purified with reverse phase HPLC H2O/CH3CN gradient w/0.1% TFA present) to afford the pure product (6-5). 1H NMR (500 MHz, CD3OD) δ 8.26 (d, 1H, J=2.3 Hz), 7.88 (d, 1H, J=8.5 Hz), 7.72 (dd, 1H, J=8.5, 2.3 Hz), 7.61 (s, 1H), 5.19-4.94 (dm, 1H, J=50.0 Hz), 3.52-3.33 (m, ˜4H, overlap w/solvent peak). LRMS m/z (M+H) 295.3 found, 295.1 required.

Workup

customThe crude was purified with reverse phase HPLC H2O/CH3CN gradient w/0.1% TFA present)

Sources & evidence

ORD record: ord-2926e3e4600e447a87afe72415ea8a63
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07501435B2

Linked notes

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