4-(1-Piperidylmethyl)phenylboronic Acid → 5-Ethyl-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1505971Notes

Reaction equation

HRID 1505971 reaction equation
Br[C:2]1[CH:18]=[N:17][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[C:9]([CH2:15][CH3:16])[C:8]=3[C:4]=2[CH:3]=1.[N:19]1([CH2:25][C:26]2[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>C(=O)([O-])[O-].[Na+].[Na+].C(#N)C.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]>[CH2:15]([C:9]1[C:8]2[C:4]3[CH:3]=[C:2]([C:29]4[CH:28]=[CH:27][C:26]([CH2:25][N:19]5[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]5)=[CH:31][CH:30]=4)[CH:18]=[N:17][C:5]=3[NH:6][C:7]=2[CH:12]=[N:11][C:10]=1[C:13]#[N:14])[CH3:16]

Participants

7

Reactant 2

HCID 230053434-(1-Piperidylmethyl)phenylboronic AcidHCID 582666243-Bromo-5-ethyl-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 582666465-Ethyl-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 46%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 3-bromo-5-ethyl-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (48 mg, 0.16 mmol), 4-piperidin-1-ylmethyl-phenyl boronic acid (56 mg, 0.26 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (12 mg, 0.016 mmol) in 2N aqueous sodium carbonate (0.5 mL) and acetonitrile (0.63 mL) was heated under microwave irradiation at 140° C. for 35 minutes. The reaction mixture was allowed to cool to ambient temperature, diluted with water (5 mL) and extracted with ethyl acetate (3×5 mL). The combined organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The resultant residue was purified by flash chromatography (silica, 2 g column, ISCO, 0-5% methanol in DCM) and trituration with diethyl ether (2×1 mL) to afford the title compound as a beige solid (29 mg, 46%). 1H NMR (DMSO-D6, 400 MHz): 12.93 (br. s, 1H), 8.99 (d, J=2.2 Hz, 1H), 8.91 (s, 1H), 8.79 (d, J=2.2 Hz, 1H), 7.79 (d, J=8.0 Hz, 2H), 7.46 (d, J=8.0 Hz, 2H), 3.53-3.43 (m, 4H), 2.42-2.33 (m, 4H), 1.55-1.47 (m, 4H), 1.46-1.37 (m, 5H). LCMS (Method A): RT=6.23 min, M+H+=396.

Workup

  1. temperatureto cool to ambient temperature
  2. extractionextracted with ethyl acetate (3×5 mL)
  3. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe resultant residue was purified by flash chromatography (silica, 2 g column, ISCO, 0-5% methanol in DCM) and trituration with diethyl ether (2×1 mL)

Sources & evidence

ORD record
ord-351c9ded76b84ac5b402bb03ff2a2215
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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