Triethylamine → HCID 67975007, compound

HRID 1472680Notes

Reaction equation

HRID 1472680 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH3:13])[CH:8]=2)[N:3]=1.[NH:14]1[CH2:19][CH2:18][CH:17]([C:20]([O:22][CH3:23])=[O:21])[CH2:16][CH2:15]1.CCN(CC)CC>CC(O)C.CCOC(C)=O>[CH3:13][O:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]([O:22][CH3:23])=[O:21])[CH2:16][CH2:15]1)[N:11]=[CH:10]2

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 424914Methyl isonipecotateHCID 592548522-Chloro-6-methoxyquinazoline2×

Product 1

HCID 67975007HCID 67975007, compoundYield 101.4%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2-chloro-6-methoxyquinazoline (Intermediate 8, 700 mg, 3.60 mmol), methyl 4-piperidinecarboxylate (2.58 g, 18.0 mmol) and Et3N (729 mg, 7.20 mmol) in iPrOH (15 mL) was heated to 50° C. for 16 hours. The reaction mixture was diluted with EtOAc (100 mL) and washed with H2O (30 mL×2) and brine (30 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by prep-HPLC (0.1% TFA as additive). Most of CH3CN was removed under reduced pressure and the remaining solvent was removed by lyophilization to give the product (1.10 g, yield: 73%).

Workup

  1. washwashed with H2O (30 mL×2) and brine (30 mL)
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give the crude product
  6. customThe crude product was purified by prep-HPLC (0.1% TFA as additive)
  7. customMost of CH3CN was removed under reduced pressure
  8. customthe remaining solvent was removed by lyophilization

Sources & evidence

ORD record
ord-78a80edf309242a69cad8296f7f5b9c2
Source dataset
uspto-grants-2015_04
Patent number
US09012646B2

Reaction notes

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