Pyridine → 1-Ethyl-3-{3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-urea

HRID 1888574Notes

Reaction equation

HRID 1888574 reaction equation
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH2:25])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=CC=CC=1.[CH2:34]([N:36]=[C:37]=[O:38])[CH3:35].C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO.O>[CH2:34]([NH:36][C:37]([NH:25][C:22]1[N:23]=[CH:24][C:19]2[NH:18][C:17]3[N:26]=[CH:27][C:14]([C:11]4[CH:12]=[CH:13][C:8]([CH2:7][N:1]5[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]5)=[CH:9][CH:10]=4)=[CH:15][C:16]=3[C:20]=2[CH:21]=1)=[O:38])[CH3:35]

Participants

8

Reactant 4

HCID 1049PyridineHCID 8022Ethyl isocyanateHCID 516892Sodium BicarbonateHCID 58266504HCID 58266504, compound

Product 1

HCID 672012941-Ethyl-3-{3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-ureaYield 31%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-amine (91.6 mg, 0.256 mmol) in DCM (9.1 mL) was treated with pyridine (22.8 μL, 0.282 mmol) and ethylisocyanate (33.2 μL, 0.423 mmol) and then the reaction mixture was heated under reflux for 5 h. The cooled reaction mixture was treated with saturated sodium bicarbonate and diluted with 20% MeOH in DCM and water. The layers were separated, the aqueous phase extracted into 20% MeOH in DCM, and the combined organic phases were dried over sodium sulfate and concentrated in vacuo. The resultant residue was purified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min) to afford the title compound as a yellow solid (34 mg, 31%). 1H NMR (DMSO-D6, 400 MHz): 9.66 (t, J=5.4 Hz, 1H), 9.19 (s, 1H), 8.96 (d, J=2.1 Hz, 1H), 8.91 (d, J=2.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 2H), 7.45 (d, J=8.1 Hz, 2H), 7.20 (s, 1H), 3.53-3.44 (m, 4H), 2.36 (m, 4H), 1.58-1.46 (m, 4H), 1.41 (m, 2H), 1.31-1.21 (m, 3H). LCMS (Method D): RT=8.06 min, M+H+=429.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 5 h
  3. customThe cooled reaction mixture
  4. customThe layers were separated
  5. extractionthe aqueous phase extracted into 20% MeOH in DCM
  6. dry with materialthe combined organic phases were dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was purified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min)

Sources & evidence

ORD record
ord-abb99bbaf0514bcb84b01efe51f2f011
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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