Diisopropylethylamine → HCID 135921431, compound

HRID 2189215Notes

Reaction equation

HRID 2189215 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[OH:18])[N:3]=1.C(N(C(C)C)CC)(C)C.[NH2:28][CH:29]1[CH2:35][CH2:34][CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]1>CC(N(C)C)=O>[NH:31]1[CH2:32][CH2:33][CH2:34][CH2:35][CH:29]([NH:28][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])[N:3]=2)[CH2:30]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 40509562-(4-Chloroquinazolin-2-yl)phenolHCID 23068067tert-Butyl 3-aminoazepane-1-carboxylate

Product 1

HCID 135921431HCID 135921431, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

2-(4-Chloroquinazolin-2-yl)phenol (0.093 g, 0.362 mmol) was dissolved in DMA (3.6 mL) and then treated with diisopropylethylamine (0.189 mL, 1.087 mmol) followed by tert-butyl 3-aminoazepane-1-carboxylate (0.078 g, 0.362 mmol) and the solution was heated at 60° C. After 18 hours, the reaction mixture was concentrated in vacuo to remove the excess amine and purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. The solvent was removed in vacuo and the residue was dissolved in methanol (0.22 mL) and treated with 4 M HCl in dioxane (0.22 mL). After 18 hours, the reaction mixture was concentrated in vacuo and purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. Further purification by silica column chromatography, eluting with a gradient of 3% to 30% methanol in dichloromethane, gave the title compound as a yellow solid (0.007 g, 6%).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customto remove the excess amine
  3. custompurified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g)
  4. washeluting with methanol
  5. customThe solvent was removed in vacuo
  6. dissolutionthe residue was dissolved in methanol (0.22 mL)
  7. additiontreated with 4 M HCl in dioxane (0.22 mL)
  8. waitAfter 18 hours
  9. concentrationthe reaction mixture was concentrated in vacuo
  10. custompurified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g)
  11. washeluting with methanol
  12. customFurther purification by silica column chromatography
  13. washeluting with a gradient of 3% to 30% methanol in dichloromethane

Sources & evidence

ORD record
ord-8399ced6a0cb4e4eac34c912b818f827
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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