Ethanol → Dichloromethane methanol ammonium hydroxide

HRID 1397756Notes

Reaction equation

HRID 1397756 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[NH:4][CH:5]=[N:6]2.[Cl:11][C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[N:14]=[C:15]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([F:33])([F:32])[F:31])[C:16]([CH2:22][NH2:23])=[N:17]2.C(N(CC)C(C)C)(C)C.[CH2:43]([OH:45])C>>[CH2:2]([Cl:1])[Cl:11].[CH3:43][OH:45].[NH4+:4].[OH-:45].[Cl:11][C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[N:14]=[C:15]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([F:33])([F:31])[F:32])[C:16]([CH2:22][NH:23][C:2]1[N:10]=[CH:9][N:8]=[C:7]3[C:3]=1[N:4]=[CH:5][NH:6]3)=[N:17]2

Participants

6

Reactant 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 53592776-ChloropurineHCID 57707823HCID 57707823, compound

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 178506133HCID 178506133, compound

Conditions

Temperature
75 °C

Procedure

A mixture of 6-chloropurine (0.147 g, 0.954 mmol), (5-chloro-3-(2-(trifluoro-methyl)phenyl)quinoxalin-2-yl)methanamine (0.3223 g, 0.954 mmol), and N,N-diisopropylethylamine (0.332 mL, 1.91 mmol) in ethanol (5.61 mL, 0.954 mmol) was stirred at 75° C. After 19 h, the mixture was removed from the heat and concentrated under reduced pressure. The residue was purified by column chromatography on a 40 g of Redi-Sep™ column using 0 to 100% gradient of EtOAc in hexane over 14 min, then 100% isocratic of EtOAc for 10 min, then 0 to 65% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 over 10 min, then 65% isocratic of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 for 10 min, then 65% to 100% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 over 4 min, and then 100% isocratic of CH2Cl2:MeOH:NH4OH (89:9:1) for 4 min as eluent to give the desired product as a brown solid. The brown solid was suspended in CH2Cl2 filtered to give N-((5-chloro-3-(2-(trifluoromethyl)phenyl)quinoxalin-2-yl)methyl)-9H-purin-6-amine as an-off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.94 (1 H, s), 7.57-8.34 (10 H, m), 4.76 (2 H, d, J=55.9 Hz); LC-MS (ESI) m/z 456.1 [M+H]+.

Workup

  1. customthe mixture was removed from the
  2. temperatureheat
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography on a 40 g of Redi-Sep™ column
  5. customover 14 min
  6. wait100% isocratic of EtOAc for 10 min
  7. wait0 to 65% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 over 10 min
  8. wait65% isocratic of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 for 10 min
  9. wait65% to 100% gradient of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2 over 4 min

Sources & evidence

ORD record
ord-9da16e9aafff4736ba1728a6f6c8e1f7
Source dataset
uspto-grants-2014_12
Patent number
US08901135B2

Reaction notes

Loading…