Sodium Bicarbonate → N,N-dimethyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)pyrimidin-2-amine

HRID 58076Notes

Reaction equation

HRID 58076 reaction equation
Br[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[CH3:15][N:16]([CH3:32])[C:17]1[N:22]=[CH:21][C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][N:18]=1.[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:11]([F:14])([F:13])[F:12])=[O:34].[CH3:15][N:16]([CH3:32])[C:17]1[N:22]=[CH:21][C:20]([C:2]2[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]3[C:3]=2[CH:4]=[N:5][NH:6]3)=[CH:19][N:18]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 16414215N,N-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amineHCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 71736822N,N-dimethyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)pyrimidin-2-amineYield 59%

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-bromo-6-(trifluoromethyl)-1H-indazole (0.1 g, 0.377 mmol), N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (0.122 g, 0.491 mmol) and PdCl2(dppf) (0.014 g, 0.019 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 30-40% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 8 minutes. The product-containing fractions were combined and the volatiles removed in vacuo to give a TFA salt of the title compound as a light brown solid (68 mg, 59%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.23 (s, 6H), 7.48 (d, J=1.01 Hz, 1H), 7.89 (s, 1H), 8.40 (d, J=0.76 Hz, 1H), 8.82 (s, 2H); ESI-MS m/z [M+H]+ calc'd for C14H12F3N5, 308.1. found 308.15.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. washeluting with a gradient of 30-40% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 8 minutes
  4. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-958876ffc7a9404fa8eb26c7e6568b4f
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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