Potassium Phosphate, Tribasic → 5-(3-(2,4-difluorophenyl)-1H-indol-5-yl)-N-methyl-1,3,4-thiadiazol-2-amine

HRID 634154Notes

Reaction equation

P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1B1OC(C)(C)C(C)(C)O1.I[C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]3[S:40][C:39]([NH:41][CH3:42])=[N:38][N:37]=3)[CH:34]=2)[NH:29][CH:28]=1>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.CC(O)C.O>[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:36]3[S:40][C:39]([NH:41][CH3:42])=[N:38][N:37]=3)[CH:34]=2)[NH:29][CH:28]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of potassium phosphate (0.089 g, 0.42 mmol), 2,4-difluorophenylboronic acid pinacol ester (0.040 g, 0.17 mmol, Aldrich), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (5 mg, 7 μmol), 5-(3-iodo-1H-indol-5-yl)-N-methyl-1,3,4-thiadiazol-2-amine (0.05 g, 0.14 mmol), and IPA/H2O (70%, 0.5 mL) was heated in a microwave at 120° C. for 10 min. The aqueous layer was removed and the organic layer was purified by preparative HPLC (10-90% MeCN/water/0.1% NH4OH) to give 5-(3-(2,4-difluorophenyl)-1H-indol-5-yl)-N-methyl-1,3,4-thiadiazol-2-amine as a tan solid. MS (ESI, pos. ion) m/z: 343 (M+1). 1H NMR (400 MHz, CD3OD) δ ppm 8.06 (1H, s), 7.64-7.73 (2H, m), 7.56-7.61 (2H, m), 7.06-7.14 (2H, m), 3.14 (3H, s).

Workup

customThe aqueous layer was removed
customthe organic layer was purified by preparative HPLC (10-90% MeCN/water/0.1% NH4OH)

Sources & evidence

ORD record: ord-6aa127c4f52e43b586efdba3defb1347
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321756B2

Reaction notes

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