Potassium Carbonate → 5-[1-(2-Methanesulfonylethyl)-piperidin-4-yloxy]-9H-diprido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60328Notes

Reaction equation

HRID 60328 reaction equation
C1(S([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:32]#[N:33])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:34]=[CH:35][CH:36]=[N:37][C:11]2=3)(=O)=O)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>CO>[CH3:31][S:28]([CH2:27][CH2:26][N:23]1[CH2:24][CH2:25][CH:20]([O:19][C:18]2[C:13]3[C:12]4[CH:34]=[CH:35][CH:36]=[N:37][C:11]=4[NH:10][C:14]=3[CH:15]=[N:16][C:17]=2[C:32]#[N:33])[CH2:21][CH2:22]1)(=[O:30])=[O:29]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 583651709-Benzenesulfonyl-5-[1-(2-methanesulfonylethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 532515295-[1-(2-Methanesulfonylethyl)-piperidin-4-yloxy]-9H-diprido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 47.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 9-benzenesulfonyl-5-[1-(2-methanesulfonylethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (6138 mg, 0.26 mmol) in methanol (10 mL) was added potassium carbonate (353 mg, 2.6 mmol) and the resultant suspension was heated to 40° C. for 3 hours. After this time, the reaction mixture was loaded directly onto a 5 g SPE NH2 cartridge, which was eluted with 1:1 methanol: dichloromethane. The appropriate fractions were concentrated in-vacuo and the resultant residue purified by flash chromatography (silica, 25 g column, Si-SPE, 0-5% 2N NH3 in methanol in dichloromethane) to afford the title compound as a pale yellow solid (49 mg, 47%). 1H NMR (400 MHz, DMSO-d6): 12.96 (s, 1H), 8.79 (s, 1H), 8.71 (dd, J=4.8, 1.6 Hz, 1H), 8.59 (dd, J=7.9, 1.6 Hz, 1H), 7.47 (dd, J=7.9, 4.8 Hz, 1H), 4.87-4.57 (m, 1H), 3.28-3.26 (m, 2H obscured by solvent peak), 3.04 (s, 3H), 3.02-2.77 (m, 2H), 2.73 (t, J=6.8 Hz, 2H), 2.20 (t, J=10.8 Hz, 2H), 2.21-1.97 (m, 2H), 1.96-1.89 (m, 2H).

Workup

  1. washwas eluted with 1:1 methanol
  2. concentrationThe appropriate fractions were concentrated in-vacuo
  3. customthe resultant residue purified by flash chromatography (silica, 25 g column, Si-SPE, 0-5% 2N NH3 in methanol in dichloromethane)

Sources & evidence

ORD record
ord-c686adb6d3f1474c8d28f41296ae5741
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

Loading…