Methanol → N-(4-methoxybenzyl)-5-(3-methyl-1H-indazol-5-yl)oxazol-2-amine

HRID 598829Notes

Reaction equation

I[C:2]1[O:3][C:4]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][N:11]=[C:10]3[CH3:16])=[CH:5][N:6]=1.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][NH2:26])=[CH:21][CH:20]=1.CN1C(=O)CCC1.CO>C(Cl)Cl>[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][NH:26][C:2]2[O:3][C:4]([C:7]3[CH:8]=[C:9]4[C:13](=[CH:14][CH:15]=3)[NH:12][N:11]=[C:10]4[CH3:16])=[CH:5][N:6]=2)=[CH:21][CH:20]=1

Participants

Conditions

Temperature: 165 °C

Procedure

A glass microwave reaction vessel was charged with 5-(2-iodooxazol-5-yl)-3-methyl-1H-indazole (0.40 g, 123 μmol), (4-methoxyphenyl)methanamine (1.13 mL, 8620 μmol) and NMP (2.0 mL). The reaction mixture was stirred and heated in a Smith Synthesizer® microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 165° C. for 10 minutes. The crude product was adsorbed onto a plug of silica gel and chromatographed through two stacked Redi-Sep® pre-packed silica gel column (12 g), eluting with a gradient of 1% to 10% 2 M NH3.MeOH in DCM, to give N-(4-methoxybenzyl)-5-(3-methyl-1H-indazol-5-yl)oxazol-2-amine (422 mg, 98% yield). LCMS (API-ES) m/z (%): 355 (100%, M++H); 1H NMR (400 MHz, MeOH-d4) 7.76 (s, 1H) 7.52 (s, 1H) 7.48-7.57 (m, 1H) 7.38-7.46 (m, 1H) 7.26-7.34 (m, 2H) 6.96-7.02 (m, 1H) 6.80-6.91 (m, 2H) 4.42 (s, 2H) 3.75 (d, J=6.06 Hz, 3H) 3.30 (s, 3H).

Workup

customA glass microwave reaction vessel
customchromatographed through two stacked Redi-Sep® pre-packed silica gel column (12 g)
washeluting with a gradient of 1% to 10% 2 M NH3

Sources & evidence

ORD record: ord-b60bace8713f478eabe1e31ef2592a7b
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07897619B2

Reaction notes

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