Bromide ion → HCID 71153115, compound

HRID 872249Notes

Reaction equation

HRID 872249 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:25]=[C:19]5[C:20]([CH3:24])=[N:21][CH:22]=[CH:23][N:18]5[N:17]=4)[CH:13]=[CH:12][N:11]3[CH:26]=2)[CH:5]=[CH:6][CH:7]=1.[CH:27]1(B(O)O)[CH2:29][CH2:28]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:27]1([C:2]2[CH:3]=[C:4]([C:8]3[N:9]=[C:10]4[CH:15]=[C:14]([C:16]5[N:25]=[C:19]6[C:20]([CH3:24])=[N:21][CH:22]=[CH:23][N:18]6[N:17]=5)[CH:13]=[CH:12][N:11]4[CH:26]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:29][CH2:28]1

Participants

9

Reactant 5

HCID 259Bromide ionHCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 71153239HCID 71153239, compound

Product 1

HCID 71153115HCID 71153115, compoundYield 75.6%

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)-8-methyl-[1,2,4]triazolo[1,5-a]pyrazine (35 mg, 0.086 mmol), cyclopropylboronic acid (22.26 mg, 0.259 mmol), TRICYCLOHEXYLPHOSPHINE (12.11 mg, 0.043 mmol), Toluene (1 mL), Water (0.3 mL) and Potassium phosphate tribasic (73.3 mg, 0.345 mmol). The solution was purged with nitrogen for 5 min and then PALLADIUM(II) ACETATE (1.939 mg, 8.64 μmol) was added. The reaction vial was sealed and heated to 110° C. for 2 hours. The reaction turned black and was then 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 1% MeOH/99% CH2Cl2. The pure fractions were combined and evaporated in vacuo affording 2-(2-(3-cyclopropylphenyl)imidazo[1,2-a]pyridin-7-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyrazine (24 mg, 0.065 mmol, 75% yield) as an off white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.67 (br. s., 1H), 8.43 (d, J=4.5 Hz, 1H), 8.25 (d, J=5.3 Hz, 1H), 8.06 (d, J=4.5 Hz, 1H), 7.95 (s, 1H), 7.82-7.68 (m, 3H), 7.35 (t, J=7.7 Hz, 1H), 7.08 (d, J=7.5 Hz, 1H), 3.01 (s, 3H), 2.08-1.97 (m, 1H), 1.09-0.96 (m, 2H), 0.90-0.75 (m, 2H), LC/Mass spec. (Method 1) RT=2.20 min. Mass=367.2 (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 1% MeOH/99% CH2Cl2
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-fa26b78414fb4bb7a83e3776e245b524
Source dataset
uspto-grants-2015_03
Patent number
US08975276B2

Reaction notes

Loading…