4-Methylmorpholine → 3-(2-Chlorophenyl)-1-isopropyl-N-[(1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1H-indazole-6-carboxamide

HRID 1047629Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]([OH:19])=O)=[CH:14][CH:15]=2)[N:10]([CH:20]([CH3:22])[CH3:21])[N:9]=1.[CH3:23][C:24]1[N:28]=[C:27]([C@H:29]([NH2:31])[CH3:30])[O:26][N:25]=1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]([NH:31][C@@H:29]([C:27]3[O:26][N:25]=[C:24]([CH3:23])[N:28]=3)[CH3:30])=[O:19])=[CH:14][CH:15]=2)[N:10]([CH:20]([CH3:22])[CH3:21])[N:9]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 3-(2-chlorophenyl)-1-isopropyl-1H-indazole-6-carboxylic acid (13.3 mg, 42.0 μmol) in N,N-dimethylformamide (0.5 mL) were added hydrochloride salt of (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethanamine (10.4 mg, 63.0 μmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (16.2 mg, 85.0 μmol), 1-hydroxy-7-azabenzotriazole (2.9 mg, 21.0 μmol) and N-methylmorpholine (18.6 μL, 0.17 mmol). The mixture was heated to 50° C. and stirred for 30 min. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the bistrifluoroacetate salt of the title compound (12 mg): HRMS [M+1] found=424.1530; 1H NMR (500 MHz, CDCl3): δ 8.12 (s, 1H); 7.75 (d, J=8.4 Hz, 1H); 7.63-7.59 (m, 1H); 7.57-7.53 (m, 1H); 7.49 (d, J=8.4 Hz, 1H); 7.39 (dd, J=5.9, 3.5 Hz, 2H); 6.84 (d, J=7.7 Hz, 1H); 5.68-5.61 (m, 1H); 5.03-4.95 (m, 1H); 2.42 (s, 3H); 1.74 (d, J=7.0 Hz, 3H); 1.67 (d, J=6.6 Hz, 6H).

Workup

customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record: ord-c59bc3ff4d1342468378479d89ac8dd8
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569512B2

Reaction notes

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