3-Chloro-2-methylaniline → 4-Chloro-1H-indazole
Reaction equation
O1CCCCC1[N:7]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][CH:12]=[C:13]2B2OC(C)(C)C(C)(C)O2)=[N:8]1.[Cl:25]C1C(C)=C(C=CC=1)N.C([O-])(=O)C.[K+].C(OC(=O)C)(=O)C.N(OCCC(C)C)=O>>[Cl:25][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:14]=1[CH:15]=[N:7][NH:8]2Participants
Procedure
Scheme 3 shows the synthesis of 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole 10 starting by cyclization of 3-chloro-2-methylaniline 11 with potassium acetate, acetic anhydride, and isoamyl nitrite to yield 4-chloro-1H-indazole 12. The indazole nitrogen of 4-chloro-1H-indazole 12 was protected as tetrahydropyranyl (THP) with 3,4-dihydro-2H-pyran, and pyridinium p-toluenesulfonate in dichloromethane to yield 4-chloro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole 13 and a minor amount (about 10%) of the THP regioisomer, 4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole. The mixture was reacted with PdCl2(PPh3)2, tricyclohexylphosphine, bis(pinacolato)diboron, and potassium acetate in DMSO and heated to 130° C. for 16 hours to give 10, containing a minor amount (about 10%) of the THP regioisomer, 1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole.
Sources & evidence
- ORD record
- ord-c0d200fa3a9f44c3ba373d092a29a386
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08431694B1
Reaction notes
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