Diisopropylethylamine → 3-(Pyridin-2-yl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1505958Notes

Reaction equation

HRID 1505958 reaction equation
Br[C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[Cl-].[Li+].CCN(C(C)C)C(C)C.C([Sn](CCCC)(CCCC)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=1)CCC.[F-].[K+]>CN(C=O)C.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>[N:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[C:2]1[CH:16]=[N:15][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 6077842-(Tributylstannyl)pyridineHCID 58266751HCID 58266751, compound

Product 1

HCID 582665223-(Pyridin-2-yl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
165 °C

Procedure

A solution of 3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (150 mg, 0.549 mmol) and lithium chloride (69.9 mg, 1.65 mmol) in DMF (0.94 mL) was treated with DIPEA (239 μL, 1.37 mmol) and 2-(tributylstannyl)pyridine (607 μL, 1.65 mmol), and then degassed by the bubbling of nitrogen for 5 minutes. Tetrakis(triphenylphosphine)palladium(0) (31.7 mg, 27.5 μmol, 5.0 mol %) was added and the mixture heated at 165° C. for 15 h. The mixture was allowed to cool and treated with saturated aqueous potassium fluoride at ambient temperature. The resulting solids were removed by filtration and washed with 20% methanol in DCM and water. The filtrate was filtered through a pad of celite, washing with 20% methanol in DCM. The layers were separated, the aqueous phase extracted into 20% methanol in DCM, and the combined organic phases concentrated in vacuo to afford a solid residue. This solid was purified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid) to afford an off-white solid powder (8.9 mg, 6.0%). 1H NMR (DMSO-D6, 400 MHz,): 13.01 (s, 1H), 9.49 (d, J=2.2 Hz, 1H), 9.43 (d, J=2.2 Hz, 1H), 9.04 (dd, J=11.6, 0.8 Hz, 2H), 8.75 (d, J=4.0 Hz, 1H), 8.15 (d, J=8.0 Hz, 1H), 7.98 (td, J=7.8, 1.8 Hz, 1H), 7.43 (dd, J=6.7, 4.9 Hz, 1H). LCMS (Method D): RT=7.26 min, M+H+=272.

Workup

  1. customdegassed by the
  2. custombubbling of nitrogen for 5 minutes
  3. temperatureto cool
  4. customThe resulting solids were removed by filtration
  5. washwashed with 20% methanol in DCM and water
  6. filtrationThe filtrate was filtered through a pad of celite
  7. washwashing with 20% methanol in DCM
  8. customThe layers were separated
  9. extractionthe aqueous phase extracted into 20% methanol in DCM
  10. concentrationthe combined organic phases concentrated in vacuo
  11. customto afford a solid residue
  12. customThis solid was purified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid)

Sources & evidence

ORD record
ord-3304e32b61ea46f9856d897306d3d75d
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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