Nitrogen → HCID 53629073, compound

HRID 493844Notes

Reaction equation

HRID 493844 reaction equation
I[C:2]1[N:3]=[C:4]([CH:12]2[CH2:15][CH:14]([N:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=12.[F:23][C:24]1[C:25](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:27]=[C:28]2[C:33]=1[N:32]=[C:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH:30]=[CH:29]2.C(=O)([O-])[O-].[Cs+].[Cs+].N#N.C([O-])(O)=O.[Na+]>COCCOC.O.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>[F:23][C:24]1[C:25]([C:2]2[N:3]=[C:4]([CH:12]3[CH2:15][CH:14]([N:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)[CH2:13]3)[N:5]3[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=23)=[CH:26][CH:27]=[C:28]2[C:33]=1[N:32]=[C:31]([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[CH:30]=[CH:29]2

Participants

9

Reactant 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 536290468-Fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinolineHCID 576810251-Iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine

Product 1

HCID 53629073HCID 53629073, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
75 °C

Procedure

A solution of 1-iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine (93 mg, 0.22 mmol), 8-fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline (87 mg, 0.25 mmol) and cesium carbonate (88 mg, 0.27 mmol) in DME (3.33 mL) and H2O (0.67 mL) was degassed with N2 for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (13 mg, 0.011 mmol) was added, and the reaction heated at 75° C. overnight. The reaction was allowed to cool to rt, poured into saturated NaHCO3 solution (50 ml) and extracted with ethyl acetate (3×50 ml). The combined organics were washed with brine (3×50 ml), dried (MgSO4), filtered and concentrated in vacuo. Flash chromatography (DCM stepping up to 5% MeOH in DCM) gave the title compound as an off-white solid; 1H NMR (CDCl3, 400 MHz) δ 8.27 (1H, d, J=8.6 Hz), 8.23 (2H, d, J=7.1 Hz), 7.99 (1H, d, J=8.8 Hz), 7.73-7.67 (2H, m), 7.55-7.48 (3H, m), 7.16 (1H, d, 5.1 Hz), 7.05 (1H, d, J=5.1 Hz), 3.46 (1H, m), 2.94 (1H, m), 2.71-2.32 (15H, m); MS (ES+): m/z 508.03 [M+]; HPLC: tR=1.71 min (MicromassZQ, polar—5 min).

Workup

  1. temperatureto cool to rt
  2. extractionextracted with ethyl acetate (3×50 ml)
  3. washThe combined organics were washed with brine (3×50 ml)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b64c65ebbe9d44e8856c97c9bd6eb7c9
Source dataset
uspto-grants-2009_05
Patent number
US07534797B2

Reaction notes

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