1-(2-Hydroxyethyl)piperazine → 4-(2-(6-(4-(2-Hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazol-5-ylthio)picolinic acid

HRID 1685360Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]2[S:11][C:12]([S:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]([OH:24])=[O:23])[CH:17]=3)=[CH:13][N:14]=2)[CH:3]=1.[N:25]1([CH2:31][CH2:32][OH:33])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.CCN(C(C)C)C(C)C>CCCCO>[OH:33][CH2:32][CH2:31][N:25]1[CH2:30][CH2:29][N:28]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][C:10]3[S:11][C:12]([S:15][C:16]4[CH:21]=[CH:20][N:19]=[C:18]([C:22]([OH:24])=[O:23])[CH:17]=4)=[CH:13][N:14]=3)[CH:3]=2)[CH2:27][CH2:26]1

Participants

Conditions

Temperature: 115 °C

Procedure

To a stirring solution of 4-(2-(6-chloro-2-methylpyrimidin-4-ylamino)thiazol-5-ylthio)picolinic acid (104 mg, 0.274 mmol) and 2-(piperazin-1-yl)ethanol (195 mg, 1.50 mmol) in n-BuOH (2 mL) was added i-Pr2NEt (0.20 mL, 1.15 mmol). The reaction was then heated to 115° C. in a sealed reaction vessel overnight. The reaction was cooled to room temperature and the solid collected by filtration, the filter cake was washed with n-BuOH then air dried to give the title material (89.5 mg, 69%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 11.59 (1H, s), 8.27 (1H, d, J=5.05 Hz), 7.71 (1H, s), 7.53 (1H, d, J=2.02 Hz), 7.07 (1H, dd, J=5.05, 2.02 Hz), 6.03 (1H, s), 4.45 (1H, t, J=4.67 Hz), 3.49 (6H, s), 2.41 (2H, t, J=6.32 Hz), 2.33 (3H, s). LC/MS (M+H)+: 474. HPLC ret. time (Condition I): 1.097 min.

Workup

temperatureThe reaction was cooled to room temperature
filtrationthe solid collected by filtration
washthe filter cake was washed with n-BuOH
customair dried

Sources & evidence

ORD record: ord-e19cd8e9b9a44f01add74c0c81518093
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148400B2

Reaction notes

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