1,4-Dioxane → HCID 89783083, compound

HRID 58085Notes

Reaction equation

HRID 58085 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]([NH2:32])=[N:26][C:27]([O:30][CH3:31])=[N:28][CH:29]=1.[O:33]1CCOCC1>C([O-])(O)=O.[Na+].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:31]([OH:30])([C:18]([F:21])([F:20])[F:19])=[O:33].[CH3:31][O:30][C:27]1[N:26]=[C:25]([NH2:32])[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 312751,4-DioxaneHCID 457897815-Bromo-2-methoxypyrimidin-4-amineHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 89783083HCID 89783083, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 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 (0.1 g, 0.320 mmol), 5-bromo-2-methoxypyrimidin-4-amine (0.131 g, 0.641 mmol) and PdCl2(dppf) (0.012 g, 0.016 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 15-25% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 5 minutes. The product-containing fractions were combined and volatiles were removed in vacuo to give a TFA salt of the title compound as light brown solid (0.029 g, 29%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.04 (s, 3H), 7.35-7.41 (m, 1H), 8.03 (s, 1H), 8.06-8.15 (m, 1H), 8.21 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C13H10F3N5O, 310.1. found 310.13.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. washeluting with a gradient of 15-25% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 5 minutes
  4. customvolatiles were removed in vacuo

Sources & evidence

ORD record
ord-8160efd0d9d64d4487637fd15c8519b7
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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