Triethylamine → HCID 24508060, compound

HRID 1192328Notes

Reaction equation

HRID 1192328 reaction equation
C(N(CC)CC)C.Cl[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=[CH:11][N:10]=1.[NH:19]1[CH2:29][CH2:28][CH:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:21][CH2:20]1>C1COCC1>[CH2:26]([O:25][C:23]([CH:22]1[CH2:28][CH2:29][N:19]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH2:20][CH2:21]1)=[O:24])[CH3:27]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 70770Ethyl 4-piperidinecarboxylateHCID 788644-Chloroquinazoline

Product 1

HCID 24508060HCID 24508060, compoundYield 92.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (12.7 mL, 91.1 mmol) was added to a solution of 4-chloro-quinazoline (5.00 g, 30.4 mmol) and ethyl isonipecotate (4.78 g, 30.4 mmol) in THF (80 mL) at ambient temperature. After being refluxed for 12 hours, the mixture was concentrated in vacuo, and the resulting residue was partitioned between DCM and aqueous 0.1 M NaOH. The separated DCM layer was dried (Na2SO4), filtered, and concentrated in vacuo. The resulting solids were suspended in Et2O and filtered to give 1-quinazolin-4-yl-piperidine-4-carboxylic acid ethyl ester (8.0 g, 28.0 mmol). This material was dissolved in EtOH (50 mL) and THF (50 mL) followed by the addition of NaOH (3.73 g, 93.4 mmol) in H2O (50 mL). After being stirred for 12 hours, the mixture was neutralized with 1.0N HCl (93.5 mL) and concentrated in vacuo. After the volatile organics are removed, a white precipitate forms in the resulting aqueous solution. The solid was filtered off and air-dried to give 1-quinazolin-4-yl-piperidine-4-carboxylic acid (6.5 g). 1H NMR (DMSO-d6, 400 MHz) δ 12.28 (bs, 1H), 8.57 (s, 1H), 7.91 (m, 1H), 7.75 (m, 2H), 7.49 (m, 1H), 4.13 (m, 2H), 3.22 (m, 2H), 2.57 (m, 1H), 1.93 (m, 2H), 1.72 (m, 2H).

Workup

  1. temperatureAfter being refluxed for 12 hours
  2. concentrationthe mixture was concentrated in vacuo
  3. customthe resulting residue was partitioned between DCM and aqueous 0.1 M NaOH
  4. dry with materialThe separated DCM layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationfiltered

Sources & evidence

ORD record
ord-616423ff52ba46d19ffe602441fe580a
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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