Sodium Bicarbonate → 6-amino-3-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)pyrimidin-4(3H)-one

HRID 58074Notes

Reaction equation

HRID 58074 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.[NH2:23][C:24]1[N:29]=[CH:28][N:27]([CH3:30])[C:26](=[O:31])[C:25]=1Br.[C:33]([O-:36])(O)=[O:34].[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:33]([OH:36])([C:18]([F:21])([F:20])[F:19])=[O:34].[NH2:23][C:24]1[N:29]=[CH:28][N:27]([CH3:30])[C:26](=[O:31])[C:25]=1[C:9]1[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[C:14]2[C:10]=1[CH:11]=[N:12][NH:13]2

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 897817376-amino-5-bromo-3-methylpyrimidin-4(3H)-oneHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 897828656-amino-3-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)pyrimidin-4(3H)-oneYield 16%

Reagents, catalysts & solvents 2

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

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 (0.05 g, 0.160 mmol), 6-amino-5-bromo-3-methylpyrimidin-4(3H)-one (0.042 g, 0.208 mmol) and PdCl2(dppf) (5.86 mg, 8.01 μmol) 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 25-35% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 4 minutes. The product-containing fractions were combined and the volatiles removed in vacuo to give a TFA salt of the title compound (8 mg, 16%). 1H NMR (400 MHz, CD3OD) δ ppm 3.45 (s, 3H), 7.33 (d, J=1.01 Hz, 1H), 7.83 (s, 1H), 7.89 (d, J=0.76 Hz, 1H), 8.19 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C13H10F3N5O, 310.1. found 310.2.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. washeluting with a gradient of 25-35% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 4 minutes
  4. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-22a2734188294e14973523a31f111926
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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