Cesium carbonate → (S)-1-(4-(cyclopropanecarbonyl)-2-methyl-6-(1-(pyrazin-2-ylmethyl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxalin-1(2H)-yl)ethanone

HRID 1485762Notes

Reaction equation

HRID 1485762 reaction equation
[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:16]4[CH:17]=[N:18][NH:19][CH:20]=4)[CH:14]=3)[N:9]([C:21](=[O:23])[CH3:22])[C@@H:8]([CH3:24])[CH2:7]2)=[O:5])[CH2:3][CH2:2]1.Cl[CH2:26][C:27]1([CH3:31])COC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:16]4[CH:17]=[N:18][N:19]([CH2:31][C:27]5[CH:26]=[N:9][CH:8]=[CH:7][N:6]=5)[CH:20]=4)[CH:14]=3)[N:9]([C:21](=[O:23])[CH3:22])[C@@H:8]([CH3:24])[CH2:7]2)=[O:5])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 791123-(Chloromethyl)-3-methyloxetaneHCID 118079873(S)-1-(4-(Cyclopropanecarbonyl)-2-methyl-6-(1H-pyrazol-4-yl)-3,4-dihydroquinoxalin-1 (2H)-yl)ethan-1-one

Product 1

HCID 118079416(S)-1-(4-(cyclopropanecarbonyl)-2-methyl-6-(1-(pyrazin-2-ylmethyl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxalin-1(2H)-yl)ethanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A 40-mL sealed tube was charged with (S)-1-(4-(cyclopropanecarbonyl)-2-methyl-6-(1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-yl)ethan-1-one (100 mg, 0.31 mmol), 3-(chloromethyl)-3-methyloxetane (100 mg, 0.83 mmol), cesium carbonate (300 mg, 0.92 mmol), and acetonitrile (10 mL). The resulting mixture was stirred overnight at 70° C. After cooling to room temperature, the reaction mixture was filtered through a short pad of celite and concentrated under vacuum. The residue was purified by Prep-HPLC with the following conditions: Column, SunFire Prep C18, 19×150 mm; mobile phase, Phase A: water (0.05% NH4HCO3), Phase B: CH3CN (12% CH3CN up to 64% in 14 min); Detector, UV220&254 nm. This afforded (S)-1-(4-(cyclopropanecarbonyl)-2-methyl-6-(1-((3-methyloxetan-3-yl)methyl)-1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-yl)ethanone (33.4 mg, 27%) as an off-white solid. 1H NMR (300 MHz, CD3OD) δ ppm 0.75-0.88 (m, 1H), 0.95-1.10 (m, 3H), 1.17 (d, J=6.30 Hz, 3H), 1.27 (s, 3H), 2.01-2.10 (m, 1H), 2.22 (s, 3H), 2.85-2.98 (m, 1H), 4.35-4.42 (m, 4H), 4.73-4.78 (m, 3H), 4.89-5.01 (m, 1H), 7.39-7.56 (m, 2H), 7.73 (s, 1H), 7.90 (s, 1H), 8.11 (s, 1H). MS (ESI, pos. ion) m/z 409 [M+H]+.

Workup

  1. customA 40-mL sealed tube
  2. temperatureAfter cooling to room temperature
  3. filtrationthe reaction mixture was filtered through a short pad of celite
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by Prep-HPLC with the following conditions
  6. waitmobile phase, Phase A: water (0.05% NH4HCO3), Phase B: CH3CN (12% CH3CN up to 64% in 14 min)

Sources & evidence

ORD record
ord-c5eb7f0229614045aaca81886725b5f5
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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