3-Cyano-4-fluorophenylboronic acid → 5-(8-Amino-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-fluorobenzonitrile

HRID 449073Notes

Reaction equation

HRID 449073 reaction equation
[CH:1]1([C:5]2[N:9]3[CH:10]=[CH:11][N:12]=[C:13]([NH2:14])[C:8]3=[C:7](I)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[C:16]([C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][C:23]=1[F:24])#[N:17]>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.COCCOC.O>[NH2:14][C:13]1[C:8]2[N:9]([C:5]([CH:1]3[CH2:4][CH2:3][CH2:2]3)=[N:6][C:7]=2[C:20]2[CH:21]=[CH:22][C:23]([F:24])=[C:18]([CH:19]=2)[C:16]#[N:17])[CH:10]=[CH:11][N:12]=1

Participants

5

Reactant 2

HCID 27579643-Cyano-4-fluorophenylboronic acidHCID 426093653-Cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amine

Product 1

HCID 669156655-(8-Amino-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-fluorobenzonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

Into a 10 mL microwave vessel were added 3-cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amine (100 mg, 0.0003 mol), 3-cyano-4-fluorophenylboronic acid (0.068 g, 0.00041 mol) potassium carbonate (88 mg, 0.00063 mol), Pd(PPh3)4 (40 my, 0.00003 mol), DME/Water (5:1) (5:1, DME:H2O, 1 mL) and the vessel was degassed 3× with N2. The reaction was microwaved on 300 watts, 100° C. for 45 min. The reaction vessel was resubjected to the microwave heating under the same conditions as before for 45 min. Purification by prep TLC using 4% MeOH in DCM eluting twice afforded 54 mg of the title compound as a yellow solid. MS (ES+): m/z 308.11 (100)[MH+]. HPLC: tR=2.14 min (Open Lynx polar—5 min).

Workup

  1. customthe vessel was degassed 3× with N2
  2. customThe reaction was microwaved on 300 watts, 100° C. for 45 min
  3. temperatureheating under the same conditions as before for 45 min
  4. customPurification by prep TLC
  5. customHPLC: tR=2.14 min (Open Lynx polar—5 min)

Sources & evidence

ORD record
ord-9851623963ca40159ae6819ebc25e693
Source dataset
uspto-grants-2013_07
Patent number
US08481733B2

Reaction notes

Loading…