Potassium Carbonate → 1''-(5-Isopropoxy-pyrimidin-2-yl)-5-(1-methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

HRID 2406350Notes

Reaction equation

HRID 2406350 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH:9]=[C:8]([C:11]2[CH:12]=[C:13]3[CH2:27][C:18]4([CH2:26][C:20]5([CH2:25][CH2:24][NH:23][CH2:22][CH2:21]5)[CH2:19]4)[O:17][C:14]3=[CH:15][N:16]=2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].Cl[C:29]1[N:34]=[CH:33][C:32]([O:35][CH:36]([CH3:38])[CH3:37])=[CH:31][N:30]=1.C(=O)([O-])[O-].[K+].[K+].CN1CCCC1=O>O>[CH:36]([O:35][C:32]1[CH:31]=[N:30][C:29]([N:23]2[CH2:22][CH2:21][C:20]3([CH2:19][C:18]4([O:17][C:14]5=[CH:15][N:16]=[C:11]([C:8]6[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][CH:7]=6)[CH:12]=[C:13]5[CH2:27]4)[CH2:26]3)[CH2:25][CH2:24]2)=[N:34][CH:33]=1)([CH3:38])[CH3:37]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 580579242-Chloro-5-(propan-2-yloxy)pyrimidineHCID 867012045-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Product 1

HCID 867012101''-(5-Isopropoxy-pyrimidin-2-yl)-5-(1-methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1'-cyclobutane-3',4''-piperidine]

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 5-(1-methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1′-cyclobutane-3′,4″-piperidine] (HCl salt; 60 mg), 2-chloro-5-isopropoxy-pyrimidine (25 mg), potassium carbonate (45 mg), and N-methyl-pyrrolidinone (2 ml) is stirred in a microwave oven at 150° C. for 20 min. After cooling to room temperature, water is added and the resulting mixture is extracted with ethyl acetate. The combined extracts are dried (Na2SO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate/methanol 5:5:0→5:5:1) to give the title compound. LC (method 3): tR=0.93 min; Mass spectrum (ESI+): m/z=526 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe resulting mixture is extracted with ethyl acetate
  3. dry with materialThe combined extracts are dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate/methanol 5:5:0→5:5:1)

Sources & evidence

ORD record
ord-8e7a1349206147d4a3489496119a2069
Source dataset
uspto-grants-2014_08
Patent number
US08809361B2

Reaction notes

Loading…