Sodium Carbonate → 4(2,4-dimethoxypyrimidin-5-yl)-6-(trifluoromethyl)-1H-indazole

HRID 58072

Reaction equation

HRID 58072 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)O1.Br[C:24]1[C:25]([O:32][CH3:33])=[N:26][C:27]([O:30][CH3:31])=[N:28][CH:29]=1.[C:34](=[O:37])([O-])[O-:35].[Na+].[Na+]>O1CCOCC1.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]>[C:34]([OH:35])([C:18]([F:21])([F:20])[F:19])=[O:37].[CH3:31][O:30][C:27]1[N:26]=[C:25]([O:32][CH3:33])[C:24]([C:9]2[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)=[CH:29][N:28]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2557195-Bromo-2,4-dimethoxypyrimidineHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 897831774(2,4-dimethoxypyrimidin-5-yl)-6-(trifluoromethyl)-1H-indazoleYield 45.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (35 mg, 0.112 mmol), 5-bromo-2,4-dimethoxypyrimidine (24.56 mg, 0.112 mmol), and PdCl2(dppf) (8.21 mg, 0.011 mmol) were dispersed in dioxane (1.5 mL). To the resulting slurry was added 2N aqueous sodium carbonate (0.112 mL, 0.224 mmol). The mixture was purged with nitrogen, heated in a microwave reactor at 130° C. for 50 minutes, and then filtered through a microfiltration frit. Dioxane was stripped with nitrogen. The resulting residue was taken up in DMSO and methanol (1:1) and was purified via preparative HPLC, eluting with a gradient of ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA). The purified fractions were collected to give a TFA salt of the title compound (8.2 mg, 23%). ESI-MS m/z [M+H]+ calc'd for C14H11F3N4O2, 325.1. found 325.2.

Workup

  1. customThe mixture was purged with nitrogen
  2. filtrationfiltered through a microfiltration frit
  3. custommethanol (1:1) and was purified via preparative HPLC
  4. washeluting with a gradient of ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)
  5. customThe purified fractions were collected

Sources & evidence

ORD record
ord-c1a4f9d86256414cb555e8b9c9efc9c1
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Linked notes

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