Potassium Carbonate → N-(tert-Butyl)-2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide

HRID 2170187Notes

Reaction equation

HRID 2170187 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[C:5]2=[C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:17]=[CH:18][N:4]2[N:3]=1.[C:25]([NH:29][S:30]([C:33]1[C:34]([CH:48]([F:50])[F:49])=[N:35][CH:36]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:38]=1)(=[O:32])=[O:31])([CH3:28])([CH3:27])[CH3:26].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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(Cl)Cl>[C:25]([NH:29][S:30]([C:33]1[C:34]([CH:48]([F:49])[F:50])=[N:35][CH:36]=[C:37]([C:2]2[N:7]=[C:6]([NH:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=3)[C:5]3=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:17]=[CH:18][N:4]3[N:3]=2)[CH:38]=1)(=[O:31])=[O:32])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 903861572-chloro-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amineHCID 90386255N-(tert-butyl)-2-(difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide

Product 1

HCID 90386127N-(tert-Butyl)-2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamideYield 71.5%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (0.500 g, 1.49 mmol) and N-(tert-butyl)-2-(difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide (0.697 g, 1.79 mmol) in 1,4-dioxane (5 mL) and water (1 mL) was added K2CO3 (0.412 g, 2.98 mmol). The reaction mixture was purged with nitrogen gas for 10 min. Then PdCl2(dppf)-CH2Cl2 (0.122 g, 0.149 mmol) was added and heated at 100° C. for 1 h in micro wave. The reaction mixture was allowed to cool to ambient temperature. The reaction mixture was filtered through CELITE® bed and the bed was washed with EtOAc (2×50 mL). The filtrate was diluted with water (50 mL) and extracted with EtOAc (100 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by CombiFlash (REDISEP®, silica gel, 40 g, 40% EtOAc/hexanes) to obtain N-(tert-butyl)-2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.600 g, 71.5% yield) as a pale yellow solid. LCMS Condition B-83: retention time 1.84 min, [M+1]=564.0. 1H NMR (400 MHz, CD3OD) δ ppm 1.26 (s, 9H), 4.94 (s, 2H), 6.81 (d, J=2.8 Hz, 1H), 7.27-7.31 (m, 1H), 7.44-7.55 (m, 3H), 7.59-7.63 (m, 4H), 7.77-7.82 (m, 2H), 8.43 (d, J=4.4 Hz, 1H), 9.19 (dd, J=2.0 Hz, J=1.2 Hz, 1H), 9.64 (d, J=2.0 Hz, 1H).

Workup

  1. customThe reaction mixture was purged with nitrogen gas for 10 min
  2. temperatureto cool to ambient temperature
  3. filtrationThe reaction mixture was filtered through CELITE® bed
  4. washthe bed was washed with EtOAc (2×50 mL)
  5. additionThe filtrate was diluted with water (50 mL)
  6. extractionextracted with EtOAc (100 mL)
  7. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by CombiFlash (REDISEP®, silica gel, 40 g, 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c368bbf66cae495e96b4723231998622
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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