2-(Piperazin-1-yl)pyridine-5-boronic acid, pinacol ester → N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[6-(1-piperazinyl)-3-pyridinyl]-1H-indazole-4-carboxamide

HRID 85424Notes

Reaction equation

HRID 85424 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[CH:37][C:38]([N:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)=[N:39][CH:40]=2)O1>>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=[C:2]([C:35]2[CH:40]=[N:39][C:38]([N:41]3[CH2:42][CH2:43][NH:44][CH2:45][CH2:46]3)=[CH:37][CH:36]=2)[CH:3]=1)=[O:15]

Participants

3

Reactant 2

HCID 162179462-(Piperazin-1-yl)pyridine-5-boronic acid, pinacol esterHCID 545964906-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

Product 1

HCID 54596558N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[6-(1-piperazinyl)-3-pyridinyl]-1H-indazole-4-carboxamide

Procedure

The title compound was prepared in a similar manner as described for example 8 from 6-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-methyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (90 mg, 0.216 mmol) and 1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (94 mg, 0.324 mmol). The product obtained from HPLC purification was treated with a saturated solution of NaHCO3, and solids that crashed out were filtered. The product was evaporated from MeOH, triturated from ether and then CH3CN. After drying in vacuum oven overnight, the final product was collected as a white solid (87 mg, 78%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.53 (br. s., 1H) 8.59-8.67 (m, 2H) 8.54 (s, 1H) 8.35 (s, 1H) 8.02-8.09 (m, 2H) 7.84 (s, 1H) 6.94 (d, J=9.09 Hz, 1H) 5.89 (s, 1H) 5.14 (dt, J=13.07, 6.47 Hz, 1H) 4.39 (br. s., 1H) 4.38 (br. s., 1H) 3.41-3.47 (m, 4H) 3.17 (s, 1H) 2.22 (s, 3H) 2.13 (s, 3H) 1.50 (s, 3H) 1.49 (s, 3H). LC-MS (ES) m/z=500.4 [M+H]+ Note: some piperinzyl proton atoms hidden under water peak.

Workup

  1. customThe product obtained from HPLC purification
  2. additionwas treated with a saturated solution of NaHCO3, and solids that
  3. filtrationcrashed out were filtered
  4. customThe product was evaporated from MeOH
  5. customtriturated from ether
  6. customAfter drying in vacuum oven overnight
  7. customthe final product was collected as a white solid (87 mg, 78%)

Sources & evidence

ORD record
ord-47a8ff23de8e47edb765d42b24124efe
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Reaction notes

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