Pyridine → 3-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl-methanesulfonamide

HRID 1888573Notes

Reaction equation

HRID 1888573 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](N)=[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.[CH3:28][S:29](Cl)(=[O:31])=[O:30].C(=O)(O)[O-].[Na+].[N:38]1C=CC=CC=1>CO.C(Cl)Cl.O>[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]([CH2:28][S:29]([NH2:38])(=[O:31])=[O:30])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 58266504HCID 58266504, compound

Product 1

HCID 866535003-(4-Piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl-methanesulfonamideYield 38%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-amine (82.1 mg, 0.230 mmol) in pyridine (8.2 mL) was treated with methanesulfonyl chloride (58.7 μL, 0.758 mmol) and heated at 50° C. for 15 h. The cooled reaction mixture was treated with saturated sodium bicarbonate solution 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 tan solid (38 mg, 38%). 1H NMR (DMSO-D6, 400 MHz): 12.03 (s, 1H), 8.96 (d, J=2.1 Hz, 1H), 8.88 (d, J=2.1 Hz, 1H), 8.64 (s, 1H), 7.85 (s, 1H), 7.77 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 3.48 (s, 2H), 3.22 (s, 3H), 2.36 (m, 4H), 1.55-1.46 (m, 4H), 1.41 (m, 2H). LCMS (Method D): RT=7.37 min, M+H+=436.

Workup

  1. customThe cooled reaction mixture
  2. customThe layers were separated
  3. extractionthe aqueous phase extracted into 20% MeOH in DCM
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. 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-a792d01bf9e94ef88fbd9a6d70561f65
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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