4-Methylmorpholine → N-[(1R)-1-(3-Methyl-1,2,4-oxadiazol-5-yl)ethyl]-3-(morpholin-4-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxamide

HRID 1047641Notes

Reaction equation

[N:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([OH:18])=O)=[CH:13][CH:14]=3)[N:9]([C:19]3[CH:23]=[CH:22][S:21][CH:20]=3)[N:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.[CH3:25][C:26]1[N:30]=[C:29]([C@H:31]([NH2:33])[CH3:32])[O:28][N:27]=1.CN1CCOCC1.ON1C2N=CC=CC=2N=N1>CN(C)C=O>[CH3:25][C:26]1[N:30]=[C:29]([C@H:31]([NH:33][C:16]([C:12]2[CH:11]=[C:10]3[C:15]([C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)=[N:8][N:9]3[C:19]3[CH:23]=[CH:22][S:21][CH:20]=3)=[CH:14][CH:13]=2)=[O:18])[CH3:32])[O:28][N:27]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 3-(morpholin-4-yl)-1-(thiophen-3-yl)-1H-indazole-6-carboxylic acid (20.0 mg, 45.0 μmol), (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine hydrochloride (18.1 mg, 90 μmol, and N-methylmorpholine (24.8 μL, 226 μmol) in N,N-dimethylformamide (226 μL) were added N-[2-(dimethylamino)ethyl]-N-ethylcarbodiimide hydrochloride (15.1 mg, 79.0 μmol), 1-hydroxy-7-azabenzotriazole (3.1 mg, 23 pawl). The mixture was stirred at 50° C. for 1 h. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% ammonium hydroxide) gave the title compound (19 mg). HRMS [M+1] found=439.1545. 1H NMR (400 MHz, DMSO-d6) δ: 9.37 (1H, d, J=7.33 Hz), 8.20 (1H, s), 8.05 (1H, d, 8.57 Hz), 7.77-7.74 (2H, m), 7.64 (1H, dd, J=8.56, 1.33 Hz), 7.56 (1H, 4.58, 2.12 Hz), 5.43-5.37 (1H, m), 3.83 (4H, t, J=4.39 Hz), 3.43 (4H, t, J=4.39 Hz), 2.33 (3H, s), 1.64 (3H, d, J=7.15 Hz).

Workup

customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% ammonium hydroxide)

Sources & evidence

ORD record: ord-34f3c321b92b4c9bb0d56abdc9d320c9
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569512B2

Reaction notes

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