Water → 5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 1972904Notes

Reaction equation

HRID 1972904 reaction equation
Br[C:2]1[CH:3]=[CH:4][N:5]2[C:10]=1[C:9]([NH2:11])=[N:8][CH:7]=[N:6]2.[CH2:12]([N:19]1[CH:27]=[C:26]2[C:21]([CH:22]=[C:23](B3OC(C)(C)C(C)(C)O3)[CH:24]=[CH:25]2)=[N:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C([O-])([O-])=O.[Na+].[Na+].O>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:12]([N:19]1[CH:27]=[C:26]2[C:21]([CH:22]=[C:23]([C:2]3[CH:3]=[CH:4][N:5]4[C:10]=3[C:9]([NH2:11])=[N:8][CH:7]=[N:6]4)[CH:24]=[CH:25]2)=[N:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 585298655-Bromopyrrolo[2,1-f][1,2,4]triazin-4-amine

Product 1

HCID 585293515-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amineYield 75%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred degassed mixture 5-bromopyrrolo[2,1-f][1,2,4]triazin-4-amine (500 mg, 2.35 mmol), Intermediate C (1.18 g, 3.52 mmol), Na2CO3 (746 mg, 7.04 mmol) and H2O (3.5 mL) in DMF (18 mL) was added tetrakis(triphenylphosphine)palladium(0) (271 mg, 0.24 mmol). The reaction was heated at 110° C. for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (50 mL) and H2O (50 mL). The layers were separated and the aqueous was further extracted with ethyl acetate (1×50 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated to dryness. The crude material was purified via ISCO® chromatography using 3:1 ethyl acetate/hexanes to afford 600 mg (75%) of the desired product, which contained trace impurities. ES-MS ink 341.23 [M+H]+, HPLC RT (min) 2.91.

Workup

  1. temperaturecooled to rt
  2. customThe mixture was partitioned between ethyl acetate (50 mL) and H2O (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous was further extracted with ethyl acetate (1×50 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to dryness
  8. customThe crude material was purified via ISCO® chromatography

Sources & evidence

ORD record
ord-422dd99d72f24491a7ab63f672e91ed4
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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