Acetic Acid → 5-(4-Methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 336401Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+].I[C:56]1[N:72]=[C:59]2[CH:60]=[CH:61][CH:62]=[C:63]([C:64]3[CH:69]=[CH:68][C:67]([O:70][CH3:71])=[CH:66][CH:65]=3)[N:58]2[N:57]=1.N#N.C(O)(=O)C>CN(C)C=O>[CH3:71][O:70][C:67]1[CH:66]=[CH:65][C:64]([C:63]2[N:58]3[N:57]=[C:56]([NH:1][C:2]4[CH:3]=[CH:4][C:5]([N:8]5[CH2:9][CH2:10][N:11]([CH3:14])[CH2:12][CH2:13]5)=[CH:6][CH:7]=4)[N:72]=[C:59]3[CH:60]=[CH:61][CH:62]=2)=[CH:69][CH:68]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 4-(4-aminophenyl)-1-methylpiperazine (163 mg, 0.86 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (54 mg, 0.11 mmol), sodium tert-butoxide (103 mg, 1 mmol), and 2-iodo-5-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine (150 mg, 0.43 mmol) in dimethylformamide (4 mL) was degassed by evacuation of the reaction vessel followed by N2 purge (3×). To this mixture was added trisdibenzylideneacetone-bispalladium (52 mg, 0.06 mmol), and the reaction mixture was further degassed. The reaction mixture was heated to 100° C. After 2 h, acetic acid (60 mg, 1 mmol) was added, the resulting mixture was filtered and concentrated. Purification by reverse phase HPLC provided product (60 mg, 30%). 1H NMR (400 MHz, CD3OD), δ: 8.10 (d, 2H), 7.7 (m, 1H), 7.6 (d, 2H), 7.35 (t, 1H), 7.20 (m, 3H), 7.0 (d, 2H), 3.9 (s, 3H), 3.2 (t, 4H), 2.7 (t, 4H), 2.4 (s, 3H); ES-MS m/z 415.3.

Workup

custompurge (3×)
filtrationthe resulting mixture was filtered
concentrationconcentrated
customPurification by reverse phase HPLC

Sources & evidence

ORD record: ord-8d029baf53484656b7df5c5fab3e5f14
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889673B2

Reaction notes

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