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

HRID 60325Notes

Reaction equation

HRID 60325 reaction equation
C1(S([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:30]#[N:31])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][CH:27]([F:29])[F:28])[CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:32]=[CH:33][CH:34]=[N:35][C:11]2=3)(=O)=O)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>CO>[F:29][CH:27]([F:28])[CH2:26][N:23]1[CH2:22][CH2:21][CH:20]([O:19][C:18]2[C:13]3[C:12]4[CH:32]=[CH:33][CH:34]=[N:35][C:11]=4[NH:10][C:14]=3[CH:15]=[N:16][C:17]=2[C:30]#[N:31])[CH2:25][CH2:24]1

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 583651179-Benzenesulfonyl-5-[1-(2,2-difluoroethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 583650065-[1-(2,2-Difluoroethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 73%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 9-benzenesulfonyl-5-[1-(2,2-difluoroethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (68 mg, 0.14 mmol) in methanol (5 mL) was added potassium carbonate (193 mg, 1.4 mmol) and the resultant suspension was heated to 40° C. for 4 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, 10 g column, Si-SPE, 0-4% 2N NH3 in methanol in dichloromethane) to afford the title compound as a pale yellow solid (36 mg, 73%). LCMS (Method C): RT=6.07 min, M+H+=358. 1H NMR (300 MHz, CD3OD): 8.74 (s, 1H), 8.64-8.64 (m, 2H), 7.58 (s, 1H), 7.43 (dd, J=7.9, 4.9 Hz, 1H), 5.94 (tt, J=55.8, 4.2 Hz, 1H), 4.93-4.92 (m, 1H), 3.11-2.99 (m, 2H), 2.82 (td, J=15.1, 4.3 Hz, 2H), 2.51-2.51 (m, 2H), 2.15-2.14 (m, 4H).

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, 10 g column, Si-SPE, 0-4% 2N NH3 in methanol in dichloromethane)

Sources & evidence

ORD record
ord-e27350a1b4d246ed9013e9bae876acdd
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

Loading…