Cesium carbonate → HCID 86712718, compound

HRID 1779082Notes

Reaction equation

HRID 1779082 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:5]([CH3:21])=[CH:4][N:3]=1.[CH3:22][N:23]1[CH:27]=[C:26]([NH2:28])[CH:25]=[N:24]1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:21][C:5]1[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([O:19][CH3:20])=[O:18])=[N:7][C:2]([NH:28][C:26]2[CH:25]=[N:24][N:23]([CH3:22])[CH:27]=2)=[N:3][CH:4]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 47709901-methyl-1H-pyrazol-4-amineHCID 86712625HCID 86712625, compound

Product 1

HCID 86712718HCID 86712718, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 2-(2-((2-chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)acetate (K7) (0.200 g, 0.665 mmol) in 1,4-dioxane (8 mL) was added 1-methyl-1H-pyrazol-4-amine (0.065 g, 0.665 mmol), Cs2CO3 (0.867 g, 2.66 mmol), Pd2(dba)3 (0.061 g, 0.067 mmol) and Xantphos (0.115 g, 0.200 mmol). The resulting mixture was degassed with nitrogen for 5 minutes before heating under microwave irradiation for 30 minutes at 120° C. The mixture was diluted with EtOAc (100 mL), washed with water (2×25 mL), brine (25 mL), dried (Na2SO4) and concentrated under reduced pressure. The resulting brown oil was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in hexanes) to give the title compound A115 as a yellow solid (0.128 g, 53%); 1H NMR (400 MHz, d6-DMSO) δ 9.47 (s, 1H), 8.39 (s, 1H), 7.89 (s, 1H), 7.67 (d, J=7.4 Hz, 1H) 7.51-7.44 (m, 3H), 7.43-7.37 (m, 1H), 3.98 (s, 2H), 3.81 (s, 3H), 3.61 (s, 3H), 2.25 (s, 3H). LCMS-A: rt 5.856 min; m/z 362 [M+H]+.

Workup

  1. customThe resulting mixture was degassed with nitrogen for 5 minutes
  2. additionThe mixture was diluted with EtOAc (100 mL)
  3. washwashed with water (2×25 mL), brine (25 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting brown oil was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2a3a3878fff74ff5a04943b154152fc2
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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