2-(4-Morpholinyl)acetohydrazide → 4-({3-[3-(4-Fluorophenyl)(1H-indazol-5-YL)]-1H-1,2,4-triazol-5-YL}methyl)morpholine

HRID 2183329Notes

Reaction equation

Cl.C(O[C:5]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][N:11]=[C:10]2[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[NH:6])C.C[O-].[Na+].[NH2:26][NH:27][C:28](=O)[CH2:29][N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>C(O)C.CO>[F:22][C:19]1[CH:18]=[CH:17][C:16]([C:10]2[C:9]3[C:13](=[CH:14][CH:15]=[C:7]([C:5]4[N:6]=[C:28]([CH2:29][N:30]5[CH2:35][CH2:34][O:33][CH2:32][CH2:31]5)[NH:27][N:26]=4)[CH:8]=3)[NH:12][N:11]=2)=[CH:21][CH:20]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A suspension of ethoxy[3-(4-fluorophenyl)(1H-indazol-5-yl)]methanimine hydrochloride (0.300 g, 0.94 mmol) in 4 mL of anhydrous ethanol was prepared and cooled to 0° C. An excess of a freshly prepared solution of sodium methoxide in methanol (1.41 mL, 2.0 M)) was added followed by 3 equivalents of N-amino-2-morpholin-4-ylacetamide (0.449 g, 2.82 mmol) as a solid. The reaction mixture was heated to reflux temperature in a sealed tube for 2 days. The reaction was then quenched with water, the pH adjusted to neutral and the crude product extracted with ethyl acetate. The components of the crude mixture were separated by preparative HPLC (title compound: 0.017 g, 5% yield): 1H NMR (CD3OD) δ 8.71 (d, 1H), 8.08-8.03 (m, 3H), 7.68 (d, 1H), 7.3 (t, 2H), 3.73 (m, 6H), 2.59 (m, 4H); ES-MS (m/z) 379 [M+H]+.

Workup

customwas prepared
temperatureThe reaction mixture was heated
temperatureto reflux temperature in a sealed tube for 2 days
customThe reaction was then quenched with water
extractionextracted with ethyl acetate
customThe components of the crude mixture were separated by preparative HPLC (title compound: 0.017 g, 5% yield)

Sources & evidence

ORD record: ord-2b7d2de351e3473a8862c0f56c33523b
Source dataset: uspto-grants-2005_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06897231B2

Reaction notes

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