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

HRID 58073Notes

Reaction equation

HRID 58073 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.I[C:24]1[C:25]([O:32][CH3:33])=[N:26][C:27]([O:30][CH3:31])=[N:28][CH:29]=1.C(=O)([O-])[O-].[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]>[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

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2634165-Iodo-2,4-dimethoxypyrimidineHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Product 1

HCID 897831774(2,4-dimethoxypyrimidin-5-yl)-6-(trifluoromethyl)-1H-indazoleYield 48.1%

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 (100 mg, 0.320 mmol), 5-iodo-2,4-dimethoxypyrimidine (57 mg, 0.215 mmol), and PdCl2(dppf) (23 mg, 0.032 mmol) were dispersed in dioxane (3 mL). To the resulting slurry was added 2N aqueous sodium carbonate (0.320 mL, 0.641 mmol). The mixture was heated in a microwave reactor at 130° C. for 1 hour, and then filtered through a microfiltration frit, which was rinsed with methanol. The solvents were removed in vacuo and the resulting residue was taken up in DMSO and methanol (1:1) and was purified via preparative HPLC, eluting with a gradient of 40-45% ACN (containing 0.1% formic acid) in H2O (containing 0.1% formic acid). The purified fractions were collected to give a formic acid salt of the title compound (33.5 mg, 32.2%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.95 (s, 3H), 4.00 (s, 3 H), 7.43 (s, 1H), 7.95 (s, 1H), 8.12 (s, 1H), 8.52 (s, 1H), 13.64 (br s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H11F3N4O2, 325.1. found 325.2.

Workup

  1. filtrationfiltered through a microfiltration frit, which
  2. washwas rinsed with methanol
  3. customThe solvents were removed in vacuo
  4. custommethanol (1:1) and was purified via preparative HPLC
  5. washeluting with a gradient of 40-45% ACN (containing 0.1% formic acid) in H2O (containing 0.1% formic acid)
  6. customThe purified fractions were collected

Sources & evidence

ORD record
ord-9692c1ca03644ae9b50cf6e893bf0511
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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