Bromide ion → HCID 71153192, compound

HRID 872250Notes

Reaction equation

HRID 872250 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[CH:15]=[C:14]([C:16]4[N:26]=[C:19]5[C:20]([CH3:25])=[N:21][CH:22]=[C:23]([CH3:24])[N:18]5[N:17]=4)[CH:13]=[CH:12][N:11]3[CH:27]=2)[CH:5]=[CH:6][CH:7]=1.[CH:28]1(B(O)O)[CH2:30][CH2:29]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Br-]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH:28]1([C:2]2[CH:3]=[C:4]([C:8]3[N:9]=[C:10]4[CH:15]=[C:14]([C:16]5[N:26]=[C:19]6[C:20]([CH3:25])=[N:21][CH:22]=[C:23]([CH3:24])[N:18]6[N:17]=5)[CH:13]=[CH:12][N:11]4[CH:27]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:30][CH2:29]1

Participants

9

Reactant 5

HCID 259Bromide ionHCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 71153203HCID 71153203, compound

Product 1

HCID 71153192HCID 71153192, compoundYield 66.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a microwave vial was added 2-(2-(3-bromophenyl)imidazo[1,2-a]pyridin-7-yl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine (37 mg, 0.088 mmol), cyclopropylboronic acid (22.74 mg, 0.265 mmol), TRICYCLOHEXYLPHOSPHINE (12.37 mg, 0.044 mmol), Toluene (1 mL), Water (0.3 mL) and potassium phosphate tribasic (74.9 mg, 0.353 mmol). The solution was purged with nitrogen for 5 min and then PALLADIUM(II) ACETATE (1.981 mg, 8.82 μmol) was added. The reaction vial was sealed and heated to 110° C. for 16 hours. The reaction turned black and was checked by LC/MS. The reaction was complete as indicated by no starting bromide being present. The reaction was cooled to rt and extracted with EtOAc 4×. The organic fractions were combined, dried over Na2SO4 and evaporated in vacuo. The crude oil was purified by silica gel chromatography eluting with 5% Acetone/95% Hexanes to 60% Acetone/40% Hexanes. The pure fractions were combined and evaporated in vacuo affording 2-(2-(3-cyclopropylphenyl)imidazo[1,2-a]pyridin-7-yl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine (24 mg, 0.058 mmol, 66.1% yield) as an off white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.79 (br. s., 1H), 8.29 (d, J=4.5 Hz, 1H), 7.97 (s, 1H), 7.92 (s, 1H), 7.81 (s, 1H), 7.78 (d, J=4.5 Hz, 1H), 7.38 (t, J=4.5 Hz, 1H), 7.10 (d, J=4.5 Hz, 1H), 2.98 (s, 3H), 2.82 (s, 3H), 2.01 (m, 1H), 1.02 (m, 2H), 0.86 (m, 2H), LC/Mass spec. (Method 1) RT=1.89 min. Mass=381.2 (MH)+.

Workup

  1. customThe solution was purged with nitrogen for 5 min
  2. customThe reaction
  3. customvial was sealed
  4. temperatureThe reaction was cooled to rt
  5. extractionextracted with EtOAc 4×
  6. dry with materialdried over Na2SO4
  7. customevaporated in vacuo
  8. customThe crude oil was purified by silica gel chromatography
  9. washeluting with 5% Acetone/95% Hexanes to 60% Acetone/40% Hexanes
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-137c19641f3a4546aa5e1ae9ea6d0af8
Source dataset
uspto-grants-2015_03
Patent number
US08975276B2

Reaction notes

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