Water → N-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)pyrimidine-4-carboxamide

HRID 58083Notes

Reaction equation

HRID 58083 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]([C:30]([NH:32][CH3:33])=[O:31])=[N:26][CH:27]=[N:28][CH:29]=1.O>O1CCOCC1.C([O-])(O)=O.[Na+].C(#N)C.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]>[CH3:33][NH:32][C:30]([C:25]1[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]=[CH:27][N:26]=1)=[O:31]

Participants

8

Reactant 3

HCID 962WaterHCID 838147435-Bromo-N-methylpyrimidine-4-carboxamideHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Product 1

HCID 89783488N-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)pyrimidine-4-carboxamideYield 12.1%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
140 °C

Procedure

A vial was charged with a mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (0.144 g, 0.463 mmol), 5-bromo-N-methylpyrimidine-4-carboxamide (0.1 g, 0.463 mmol) and PdCl2(dppf) (0.017 g, 0.023 mmol) in dioxane (8 mL) and aqueous saturated NaHCO3 (2 mL). The resulting light brown suspension was heated at 140° C. for 45 minutes in a microwave reactor. The reaction mixture was subsequently concentrated and the crude residue was purified by preparative HPLC, eluting with a gradient of 25-30% ACN in H2O (containing 10 mMol NH4HCO3) over a period of 8 minutes. The product-containing fractions were combined and the solvent was removed via rotary evaporation. The crude product was extracted into DCM and was washed with water. The volatiles were removed in vacuo to give the title compound as a white solid (0.018 g, 0.056 mmol, 12%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.62 (d, J=4.80 Hz, 3H), 7.43 (s, 1H), 8.04 (s, 1H), 8.01 (s, 1H), 8.89 (d, J=4.29 Hz, 1H), 9.09 (s, 1H), 9.38 (s, 1H), 13.72 (br s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H10F3N5O, 322.1. found 322.2.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. customthe solvent was removed via rotary evaporation
  4. extractionThe crude product was extracted into DCM
  5. washwas washed with water
  6. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-11e81616bad945e0bf2b2b8339498d36
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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