Diisopropylethylamine → 6-Bromo-N-[6-(4-hydroxyphenyl)-1H-indazol-4-yl]-2-pyridinecarboxamide

HRID 1695757Notes

Reaction equation

O1CCCCC1[N:7]1[CH:15]=[C:14]2[C:9]([CH:10]=[C:11]([C:17]3[CH:22]=[CH:21][C:20]([O:23]C4CCCCO4)=[CH:19][CH:18]=3)[CH:12]=[C:13]2[NH2:16])=[N:8]1.[Br:30][C:31]1[N:36]=[C:35]([C:37](O)=[O:38])[CH:34]=[CH:33][CH:32]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:30][C:31]1[N:36]=[C:35]([C:37]([NH:16][C:13]2[CH:12]=[C:11]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)[CH:10]=[C:9]3[C:14]=2[CH:15]=[N:7][NH:8]3)=[O:38])[CH:34]=[CH:33][CH:32]=1

Participants

Conditions

Temperature: 70 °C

Procedure

2-(Tetrahydro-2H-pyran-2-yl)-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-2H-indazol-4-amine (500 mg, 1.27 mmol), 6-bromo-2-pyridinecarboxylic acid (272 mg, 1.35 mmol), HATU (531 mg, 1.35 mmol) and DIPEA (0.442 ml, 2.54 mmol) were combined in DMF (10 ml) and heated at 70° C. overnight. The solvent was removed in vacuo and the residue was purified by silica gel chromatography, eluting with DCM:MeOH:ammonia. Appropriate fractions were combined and the solvent was removed in vacuo. The residue was dissolved in Methanol (20 ml) and 4 M HCl in dioxane (2 ml) and stirred at RT for 5 days. A small amount of the reaction mixture was removed (2 ml), the solvent was removed in vacuo and the residue purified by MDAP (Method B) to give the title compound.

Workup

customThe solvent was removed in vacuo
customthe residue was purified by silica gel chromatography
washeluting with DCM
customthe solvent was removed in vacuo
dissolutionThe residue was dissolved in Methanol (20 ml)
customA small amount of the reaction mixture was removed (2 ml)
customthe solvent was removed in vacuo
customthe residue purified by MDAP (Method B)

Sources & evidence

ORD record: ord-de44e72d25b240a8bfec4b31305eaf2a
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163743B2

Reaction notes

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