Dimethylformamide → N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(pyrimidin-5-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79464Notes

Reaction equation

HRID 79464 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH2:31][CH3:32])=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.CN(C)C=O.[N:38]1[CH:43]=[C:42](B(O)O)[CH:41]=[N:40][CH:39]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:31]([C:16]1[C:15]2[C:19](=[CH:20][CH:21]=[CH:22][C:14]=2[NH:13][C:11]([C:8]2[N:5]3[CH:6]=[CH:7][C:2]([C:42]4[CH:43]=[N:38][CH:39]=[N:40][CH:41]=4)=[CH:3][C:4]3=[N:10][CH:9]=2)=[O:12])[N:18]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=2)[N:17]=1)[CH3:32]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 672595577-Bromo-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 67260638N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(pyrimidin-5-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 75.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

7-Bromo-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (0.06 g, 0.12 mmol) (Example 127) was dissolved in a 1:1 mixture of dimethoxyethane:dimethylformamide (0.6 mL) in a 2 dram vial. Pyrimidin-5-ylboronic acid (0.02 g, 0.18 mmol), PdCl2(dppf)*dcm (0.005 g, 0.006 mmol), and 2 M sodium carbonate solution (0.17 mL, 0.34 mmol) were added. Nitrogen was bubbled through the reaction mixture for 5 minutes before sealing the vial and heating at 90° C. for 16 hours. The reaction mixture was filtered over a 25 mm nylon filter 0.2 μM. The solids were washed with dimethylformamide (1 mL). The filtrate was concentrated under reduced pressure and dried under high vacuum to give N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(pyrimidin-5-yl)imidazo[1,2-a]pyridine-3-carboxamide (44 mg) as a beige solid. MS (APCI), positive scan, m/z=489.2 (M+H).

Workup

  1. customNitrogen was bubbled through the reaction mixture for 5 minutes
  2. filtrationThe reaction mixture was filtered over a 25 mm nylon
  3. filtrationfilter 0.2 μM
  4. washThe solids were washed with dimethylformamide (1 mL)
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-252a9c9ae03e445490b64f7da25d7e04
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

Loading…