3-(N,N-Dimethylaminomethyl)phenylboronic acid, pinacol ester → 6-(3-((dimethylamino)methyl)phenyl)-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

HRID 1476406Notes

Reaction equation

HRID 1476406 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.[CH3:27][N:28]([CH3:45])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=1>>[CH3:27][N:28]([CH2:29][C:30]1[CH:31]=[C:32]([C:2]2[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]3[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=3[CH3:24])=[O:15])[C:5]3[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=3[CH:10]=2)[CH:33]=[CH:34][CH:35]=1)[CH3:45]

Participants

3

Reactant 2

HCID 38036203-(N,N-Dimethylaminomethyl)phenylboronic 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 545968406-(3-((dimethylamino)methyl)phenyl)-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

Procedure

The title compound was prepared in a similar manner as described for example 12 from 6-bromo-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-methyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (100 mg, 0.240 mmol) and dimethyl{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}amine (93 mg, 0.312 mmol). The product obtained from HPLC purification was treated with a saturated solution of NaHCO3, solids that crashed out were filtered, and air-dried for 15 min. The product was then triturated first from EtOAc (containing EtOH) and then hexanes. The solid was then concentrated from MeOH, and triturated with ether, and then dried in vacuum oven overnight. The product was collected as a white solid (56 mg, 56%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.53 (s, 1H) 8.66 (t, J=4.93 Hz, 1H) 8.37 (s, 1H) 8.09 (s, 1H) 7.83 (s, 1H) 7.71-7.76 (m, 2H) 7.46 (t, J=7.96 Hz, 1H) 7.33 (d, J=7.58 Hz, 1H) 5.89 (s, 1H) 5.19 (quin, J=6.63 Hz, 1H) 4.40 (s, 1H) 4.39 (s, 1H) 3.49 (s, 2H) 2.22 (s, 3H) 2.19 (s, 6H) 2.12 (s, 3H) 1.51 (s, 3H) 1.49 (s, 3H); LC-MS (ES) m/z=472.2 [M+H]+

Workup

  1. customThe product obtained from HPLC purification
  2. additionwas treated with a saturated solution of NaHCO3, solids that
  3. filtrationcrashed out were filtered
  4. customair-dried for 15 min
  5. customThe product was then triturated first from EtOAc (containing EtOH)
  6. concentrationThe solid was then concentrated from MeOH
  7. customtriturated with ether
  8. customdried in vacuum oven overnight
  9. customThe product was collected as a white solid (56 mg, 56%)

Sources & evidence

ORD record
ord-d8e52bc7eaeb4f0292d9591177471bd7
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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