Sodium Carbonate → 2-(2-(1-methyl-1H-pyrazol-4-yl)benzyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

HRID 41579

Reaction equation

HRID 41579 reaction equation
Br[C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][CH2:8][C:7]2([CH2:15][CH2:14][N:13]([C:16]3[CH:25]=[N:24][C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[N:17]=3)[CH2:12][CH2:11]2)[C:6]1=[O:26].[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC.O.CCO>[CH3:31][N:32]1[CH:36]=[C:35]([C:2]2[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=2[CH2:4][N:5]2[CH2:10][CH2:9][CH2:8][C:7]3([CH2:15][CH2:14][N:13]([C:16]4[CH:25]=[N:24][C:23]5[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=5)[N:17]=4)[CH2:12][CH2:11]3)[C:6]2=[O:26])[CH:34]=[N:33]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 672525442-(2-Bromobenzyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one

Product 1

HCID 532597922-(2-(1-methyl-1H-pyrazol-4-yl)benzyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-oneYield 194.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
120 °C

Procedure

The mixture of 2-(2-bromobenzyl)-9-(quinoxalin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one (58 mg, 0.11 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole [761446-44-0] (34 mg, 0.16 mmol), (Ph3P)2PdCl2 and sodium carbonate (39 mg, 0.37 mmol) in the solvent mixture DME/H2O/EtOH (2 ml, 7:3:2) was placed in a microwave tube. The tube was sealed and the suspension was heated at 120° C. over 1 h under microwave conditions. The reaction mixture was concentrated under reduced pressure. Methanol was added and the mixture filtered through PL-thiol MP SPE cartridge (previously washed with MeOH) and evaporated to give 100 mg of a yellow oil which was purified by preparative HPLC (column Waters Sunfire C18, 5 um, 4.6×50 mm, flow 5 ml/min, solvent A: Water+0.1% TFA; Solvent B: Acetonitrile+0.1% TFA/gradient 5-100% B in 2.5 min). The product containing fractions were adjusted to pH 7 with aqueous sodium bicarbonate an extracted with ethyl acetate to yield the title compound (35 mg, 66%). [1H NMR (600 MHz, DMSO-d6) ppm 8.84 (s, 1H), 7.92 (s, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.54-7.64 (m, 3H), 7.32-7.42 (m, 2H), 7.22-7.31 (m, 2H), 7.02-7.11 (m, 1H), 4.59 (s, 2H), 4.22-4.34 (m, 2H), 3.44 (t, J=11.1 Hz, 2H), 3.13 (t, J=5.9 Hz, 2H), 2.02-2.13 (m, 2H), 1.86-1.95 (m, 2H), 1.75-1.85 (m, 2H), 1.61 (d, J=13.5 Hz, 2H); LCMS RtC=3.11 min, [M+H]+=467.2].

Workup

  1. customwas placed in a microwave tube
  2. customThe tube was sealed
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionMethanol was added
  5. filtrationthe mixture filtered through PL-thiol MP SPE cartridge (
  6. washpreviously washed with MeOH) and
  7. customevaporated

Sources & evidence

ORD record
ord-9b8c67d8361d41faa92cadbad54f2f0d
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Linked notes

Loading…