Triethylamine → HCID 178424197, compound

HRID 216761Notes

Reaction equation

HRID 216761 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH3:18])[C:8]([CH2:19][NH2:20])=[CH:7]2.[NH2:21][C:22]1[N:30]=[C:29]2[C:25]([NH:26][CH:27]=[N:28]2)=[C:24](Cl)[N:23]=1.C(N(CC)CC)C>CC(O)C>[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH3:18])[C:8]([CH2:19][NH:20][C:24]1[N:23]=[C:22]([NH2:21])[N:30]=[C:29]3[C:25]=1[N:26]=[CH:27][NH:28]3)=[CH:7]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 53603492-Amino-6-chloropurineHCID 57707793(8-Methyl-2-o-tolylquinolin-3-yl)methanamine

Product 1

HCID 178424197HCID 178424197, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (8-methyl-2-o-tolylquinolin-3-yl)methanamine (40 mg, 0.15 mmol), 2-amino-6-chloropurine (52 mg, 0.30 mmol), and triethylamine (42 μL, 0.30 mmol) in i-PrOH (0.8 mL) was heated in a microwave reactor at 150° C. four times for 20 min. The mixture was partitioned between saturated aqueous NaHCO3 (15 mL) and EtOAc (15 mL), the layers were separated, and the aqueous layer was extracted with EtOAc (2×15 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting yellow oil was dissolved in CH2Cl2, evaporated onto silica gel, and purified by flash chromatography (Biotage® Si 25+M) eluting with MeOH/CH2Cl2 (5% to 10%) to provide a white solid. The compound was further purified by reversed-phase HPLC (Gilson) eluting with H2O/MeCN/TFA to provide a white solid [PI3Kδ IC50=82 nM]. MS (ESI+) m/z=396.2 (M+1).

Workup

  1. customThe mixture was partitioned between saturated aqueous NaHCO3 (15 mL) and EtOAc (15 mL)
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×15 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting yellow oil was dissolved in CH2Cl2
  7. customevaporated onto silica gel
  8. custompurified by flash chromatography (Biotage® Si 25+M)
  9. washeluting with MeOH/CH2Cl2 (5% to 10%)
  10. customto provide a white solid
  11. customThe compound was further purified by reversed-phase HPLC (Gilson)
  12. washeluting with H2O/MeCN/TFA
  13. customto provide a white solid [PI3Kδ IC50=82 nM]

Sources & evidence

ORD record
ord-ad89d922912c418a9509fa563a5512d7
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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