Dimethylformamide → 5-(1-Ethylpiperidin-4-yloxy)-9H-dipyrido[2,3-b:4',3'-d]pyrrole-3,6-dicarbonitrile

HRID 1505991Notes

Reaction equation

HRID 1505991 reaction equation
[CH3:1][N:2](C=O)C.C1(S([N:15]2[C:19]3[CH:20]=[N:21][C:22]([C:33]#[N:34])=[C:23]([O:24][CH:25]4[CH2:30][CH2:29][N:28]([CH2:31][CH3:32])[CH2:27][CH2:26]4)[C:18]=3[C:17]3[CH:35]=[C:36](Br)[CH:37]=[N:38][C:16]2=3)(=O)=O)C=CC=CC=1.C(N(CC)CC)C>C(=O)(O)[O-].[Na+].[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:31]([N:28]1[CH2:27][CH2:26][CH:25]([O:24][C:23]2[C:18]3[C:17]4[CH:35]=[C:36]([C:1]#[N:2])[CH:37]=[N:38][C:16]=4[NH:15][C:19]=3[CH:20]=[N:21][C:22]=2[C:33]#[N:34])[CH2:30][CH2:29]1)[CH3:32]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 582668389-Benzenesulfonyl-3-bromo-5-(1-ethyl-piperidin-4-yloxy)-9H-dipyrido[2,3-b:4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 582668395-(1-Ethylpiperidin-4-yloxy)-9H-dipyrido[2,3-b:4',3'-d]pyrrole-3,6-dicarbonitrileYield 5%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
150 °C

Procedure

DMF (8 mL) was added to a mixture of 9-benzenesulfonyl-3-bromo-5-(1-ethyl-piperidin-4-yloxy)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (200 mg, 0.37 mmol), zinc cyanide (217 mg, 1.85 mmol) and tetrakis(triphenylphosphine) palladium(0) (43 mg, 0.04 mmol) and the reaction mixture heated under microwave irradiation at 150° C. for 30 min. Triethylamine (2 mL) was then added and the reaction mixture heated at 50° C. for 24 h. The mixture was diluted with saturated aqueous sodium bicarbonate solution (100 mL) and extracted into 10% MeOH in DCM (2×25 mL). The combined organic phase was adsorbed onto HM-N then purified by flash chromatography (silica, 12 g column, ISCO, 0-10% MeOH in DCM) to afford the title compound as a cream solid (6 mg, 5%). 1H NMR (DMSO-D6, 400 MHz): 9.07 (d, J=2.0 Hz, 1H), 8.99 (d, J=1.9 Hz, 1H), 8.84 (s, 1H), 4.86-4.76 (m, 1H), 2.97-2.87 (m, 2H), 2.42 (q, J=7.2 Hz, 2H), 2.23-2.13 (m, 2H), 2.12-1.94 (m, 4H), 1.03 (t, J=7.2 Hz, 3H). LCMS (Method H): RT=5.27 min, M+H+=347.

Workup

  1. temperaturethe reaction mixture heated at 50° C. for 24 h
  2. extractionextracted into 10% MeOH in DCM (2×25 mL)
  3. customthen purified by flash chromatography (silica, 12 g column, ISCO, 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-149204ecb93b4ea9a8f5e2d2b32e7773
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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