Cesium carbonate → ethyl 4-({2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridine-3-carboxylate

HRID 1776443Notes

Reaction equation

HRID 1776443 reaction equation
[CH2:1]([O:3][C:4]1[CH:28]=[C:27]([F:29])[C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]3[N:23]=[C:22]([NH2:24])[C:21]([O:25][CH3:26])=[CH:20][N:19]=3)=[N:10]2)=[C:6]([F:30])[CH:5]=1)[CH3:2].Cl[C:32]1[C:37]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:36][N:35]=[CH:34][CH:33]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([F:30])[C:7]([CH2:8][N:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]3[N:23]=[C:22]([NH:24][C:32]4[CH:33]=[CH:34][N:35]=[CH:36][C:37]=4[C:38]([O:40][CH2:41][CH3:42])=[O:39])[C:21]([O:25][CH3:26])=[CH:20][N:19]=3)=[N:10]2)=[C:27]([F:29])[CH:28]=1)[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 14116704Ethyl 4-chloropyridine-3-carboxylateHCID 867324712-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-amine

Product 1

HCID 86732470ethyl 4-({2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

150 mg of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxypyrimidin-4-amine (1-4-3, 0.365 mmol, 1.0 eq.), 89 mg of commercial ethyl 4-chloronicotinate (0.401 mmol, 1.1 eq.), 31.6 mg of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.055 mmol, 0.15 eq.), 356 mg of caesium carbonate (1.09 mmol, 3.0 eq.) and 8.2 mg of palladium diacetate (0.036 mmol, 0.1 eq.) were suspended in 4.7 mL of dry dioxane and stirred under nitrogen atmosphere at 105° C. bath temperature for 3 h. Solids were filtered off, washed with dioxane and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography yielding 77 mg from which only 15.7 mg were further purified by crystallization from THF to yield 3.1 mg (0.01 mmol, 1.44%) of analytically pure target compound.

Workup

  1. filtrationSolids were filtered off
  2. washwashed with dioxane
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by flash chromatography
  5. customyielding 77 mg from which only 15.7 mg
  6. customwere further purified by crystallization from THF
  7. customto yield 3.1 mg (0.01 mmol, 1.44%) of analytically pure target compound

Sources & evidence

ORD record
ord-5f868cad9cd8404e87a93e98f64fa04a
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

Loading…