4-Bromopyridinium chloride → 5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

HRID 1776392Notes

Reaction equation

HRID 1776392 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH2:27])=[N:5][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[N:10]=2)=[N:7][CH:8]=1.Cl.Br[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1.CC([O-])(C)C.[Na+]>CN(C=O)C.ClCCl.C1(/C=C/C(=O)/C=C/C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:1][O:2][C:3]1[C:4]([NH:27][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)=[N:5][C:6]([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[N:10]=2)=[N:7][CH:8]=1

Participants

7

Reactant 3

HCID 881004-Bromopyridinium chloride2×HCID 23676156Sodium t-butoxide2×HCID 867324165-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amine

Product 1

HCID 867324175-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine

Reagents, catalysts & solvents 3

HCID 15673654(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one palladiumCatalyst2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

205 mg of 5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amine (1-4-1, 0.568 mmol, 1 eq.), 121.6 mg of 4-bromopyridine hydrochloride (1:1) (0.625 mmol. 1.1 eq.), 136.5 mg of sodium 2-methylpropan-2-olate (1.42 mmol, 2.5 eq.), 106.2 mg of 1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (0.171 mmol, 0.3 eq.) and 52.0 mg of (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) (0.057 mmol, 0.1 eq.) were suspended in 3 ml of dry DMF under nitrogen atmosphere. The reaction mixture was stirred for two days at 100° C. 122 mg of 4-bromopyridine hydrochloride (1:1) (0.625 mmol. 1.1 eq.), 137 mg of sodium 2-methylpropan-2-olate (1.42 mmol, 2.5 eq.), 106 mg of 1′-binaphthalene-2,2′-diylbis(diphenylphosphane) (0.171 mmol, 0.3 eq.) and 52.0 mg of (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) (0.057 mmol, 0.1 eq.) were added and stirred for further 24 hours. The mixture was cooled down to room temperature, diluted with 10 ml dichloromethane and filtered off. The filtrate was concentrated in vacuo. The residue was purified by flash chromatography to yield 126 mg (0.23 mmol, 81%) of the analytically pure target compound.

Workup

  1. stirringstirred for further 24 hours
  2. temperatureThe mixture was cooled down to room temperature
  3. filtrationfiltered off
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by flash chromatography
  6. customto yield 126 mg (0.23 mmol, 81%) of the analytically pure target compound

Sources & evidence

ORD record
ord-090713e78eb3411ab218e958c45e3687
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

Loading…