Bromide ion → HCID 71153117, compound

HRID 872251Notes

Reaction equation

HRID 872251 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.[NH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[Br-]>[NH4+].[Cl-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:24][C:23]1[N:18]2[N:17]=[C:16]([C:14]3[CH:13]=[CH:12][N:11]4[CH:27]=[C:8]([C:4]5[CH:5]=[CH:6][CH:7]=[C:2]([N:28]6[CH2:32][CH2:31][CH2:30][CH2:29]6)[CH:3]=5)[N:9]=[C:10]4[CH:15]=3)[N:26]=[C:19]2[C:20]([CH3:25])=[N:21][CH:22]=1

Participants

9

Reactant 5

HCID 259Bromide ionHCID 31268PyrrolidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 71153203HCID 71153203, compound

Product 1

HCID 71153117HCID 71153117, compoundYield 54.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
100 °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), pyrrolidine (18.83 mg, 0.265 mmol), SODIUM TERT-BUTOXIDE (29.7 mg, 0.309 mmol), BINAP (5.49 mg, 8.82 mmol), and Toluene (1 mL). The solution was purged with nitrogen for 5 min and then PALLADIUM(II) ACETATE (0.991 mg, 4.41 mmol) was added. The reaction vial was sealed and heated to 100° C. for 16 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 diluted with saturated NH4Cl 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 5,8-dimethyl-2-(2-(3-(pyrrolidin-1-yl)phenyl)imidazo[1,2-a]pyridin-7-yl)-[1,2,4]triazolo[1,5-a]pyrazine (21.9 mg, 0.048 mmol, 53.9% yield) as a tan solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.71 (s, 1H), 8.23 (dd, J=7.0, 1.5 Hz, 1H), 7.96-7.92 (m, 1H), 7.89 (d, J=1.0 Hz, 1H), 7.78 (dd, J=7.0, 1.5 Hz, 1H), 7.35-7.28 (m, 2H), 7.26-7.18 (m, 1H), 6.66-6.54 (m, 1H), 3.48-3.33 (m, 4H), 2.97 (s, 3H), 2.80 (s, 3H), 2.06 (m, 4H), LC/Mass spec. (Method 1) RT=2.32 min. Mass=410.2 (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-8368b41baa5245388399b1d7f7c6735c
Source dataset
uspto-grants-2015_03
Patent number
US08975276B2

Reaction notes

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