Acetonitrile → 6-(Pyrrolidinylcarbonyl)-3-[4-(4-methylpiperizin-1-yl)-phenyl]-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1506011Notes

Reaction equation

HRID 1506011 reaction equation
[N:1]1([C:6]([C:8]2[N:16]=[CH:15][C:14]3[NH:13][C:12]4[N:17]=[CH:18][C:19](Br)=[CH:20][C:11]=4[C:10]=3[CH:9]=2)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:22](#[N:24])[CH3:23]>C(=O)([O-])[O-].[Na+].[Na+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:1]1([C:6]([C:8]2[N:16]=[CH:15][C:14]3[NH:13][C:12]4[N:17]=[CH:18][C:19]([C:9]5[CH:10]=[CH:14][C:22]([N:24]6[CH2:4][CH2:5][N:1]([CH3:6])[CH2:2][CH2:3]6)=[CH:23][CH:8]=5)=[CH:20][C:11]=4[C:10]=3[CH:9]=2)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 6342AcetonitrileHCID 582665346-(Pyrrolidinylcarbonyl)-3-bromo-9H-dipyrido[2,3-b:4',3'-d]pyrrole

Product 1

HCID 582665466-(Pyrrolidinylcarbonyl)-3-[4-(4-methylpiperizin-1-yl)-phenyl]-9H-dipyrido[2,3-b;4',3'-d]pyrroleYield 5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
120 °C

Procedure

A degassed mixture of 6-(pyrrolidinylcarbonyl)-3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (158 mg, 0.457 mmol), 4-(4-methylpiperizin-1-yl)-phenyl-1-boronic acid, pinacol ester (597 mg, 1.98 mmol), and bis(triphenylphosphine)palladium(II) chloride (69.0 mg, 99.0 μmol, 5.0 mol %) in acetonitrile (2.5 mL) and 1.0M aqueous sodium carbonate (2.5 mL) was heated under microwave irradiation at 120° C. for 10 minutes, allowed to cool, and partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate filtered and concentrated in vacuo. The resultant residue was purified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid) to afford an off-white solid (10.0 mg, 5%). 1H NMR (DMSO-D6, 400 MHz) 12.39-12.29 (s, 1H), 9.01 (d, J=2.2 Hz, 1H), 8.88 (d, J=2.2 Hz, 31), 8.86 (s, 1H), 8.70 (s, 1H), 7.69 (d, J=8.7 Hz, 2H), 7.08 (d, J=8.8 Hz, 2H), 3.78 (t, J=6.2 Hz, 2H), 3.57 (t, J=6.2 Hz, 2H), 3.25-3.18 (m, 4H), 2.47 (m, 311), 2.24 (m, 4H), 1.87 (m, 4H). LCMS (Method D): RT=7.36 min, M+H+=441.

Workup

  1. temperatureto cool
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid)

Sources & evidence

ORD record
ord-91943b5d8451408681edf7e854c3b541
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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