Nitrogen → 5-[5-Amino-2-(2,4-difluorophenoxyl)phenyl]-7-methylimidazo[1,5-a]pyrazin-8-one

HRID 575617Notes

Reaction equation

HRID 575617 reaction equation
Br[C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[C:5](=[O:11])[N:4]([CH3:12])[CH:3]=1.[F:13][C:14]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:15]=1[O:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][C:18]=1B1OC(C)(C)C(C)(C)O1.C([O-])(O)=O.[Na+].N#N>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:21][C:20]1[CH:22]=[CH:23][C:17]([O:16][C:15]2[CH:33]=[CH:34][C:35]([F:37])=[CH:36][C:14]=2[F:13])=[C:18]([C:2]2[N:7]3[CH:8]=[N:9][CH:10]=[C:6]3[C:5](=[O:11])[N:4]([CH3:12])[CH:3]=2)[CH:19]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 516892Sodium BicarbonateHCID 896576134-(2,4-Difluorophenoxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 1180225995-Bromo-7-methylimidazo[1,5-a]pyrazin-8(7h)-one

Product 1

HCID 1180221575-[5-Amino-2-(2,4-difluorophenoxyl)phenyl]-7-methylimidazo[1,5-a]pyrazin-8-oneYield 60%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-bromo-7-methylimidazo[1,5-a]pyrazin-8-one (114.0 mg, 0.5 mmol), the title compound of Example 57, step 1 (208.0 mg, 0.6 mmol), Pd(dppf)2Cl2 (37.0 mg, 0.05 mmol), NaHCO3 (126.0 mg, 1.5 mmol) in dioxane (10 mL) and H2O (1 mL) was stirred in microwave at 110° C. with N2 atmosphere for 3 hours. The solvent was evaporated to give the crude product, which was purified by column chromatography (PE:EA=3/1) to give the title compound (110 mg, 60%) as a yellow solid. 1H NMR (CDCl3 400 MHz) δ 7.94 (s, 1H), 7.82 (s, 1H), 6.93-6.82 (m, 2H), 6.79-6.74 (m, 4H), 6.41 (s, 1H), 3.50 (s, 3H). LCMS (M+H)+ 369.

Workup

  1. customThe solvent was evaporated
  2. customto give the crude product, which
  3. customwas purified by column chromatography (PE:EA=3/1)

Sources & evidence

ORD record
ord-b410b430ce60403aa951838e5fdc8cf1
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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