4-Quinazolin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid benzyl ester → 4-(1,2,3,6-Tetrahydro-pyridin-4-yl)-quinazoline

HRID 1192392Notes

Reaction equation

HRID 1192392 reaction equation
C(OC([N:11]1[CH2:16][CH:15]=[C:14]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH2:13][CH2:12]1)=O)C1C=CC=CC=1>CO.[Pd]>[NH:11]1[CH2:12][CH:13]=[C:14]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH2:15][CH2:16]1

Participants

4

Reactant 1

HCID 675400354-Quinazolin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid benzyl ester

Product 1

HCID 675388824-(1,2,3,6-Tetrahydro-pyridin-4-yl)-quinazolineYield 64.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of 4-Quinazolin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid benzyl ester (0.907 g, 2.63 mmol) in MeOH (30 mL) under N2 was cautiously added 10% Pd on carbon (100 mg). The reaction was hydrogenated at 50 psi using a parr shaker for 3 days. The catalyst was removed by filtration. The filtrate was evaporated under vacuum. The resulting residue was purified by column chromatography (DCM:MeOH, 20:1 to DCM:MeOH:Et3N, 100:10:1) to give 4-(1,2,3,6-Tetrahydro-pyridin-4-yl)-quinazoline (0.358 g, 64%) as a white waxy solid. 1H NMR (CDCl3, 400 MHz) δ 9.27 (s, 1H), 8.19 (d, J=8.4 Hz, 1H), 8.06 (d, J=8.4 Hz, 1H), 7.88 (t, J=8.4 Hz, 1H), 7.65 (t, J=8.4 Hz, 1H), 3.71 (m, 1H), 3.31 (m, 2H), 2.90 (m, 2H), 1.99 (m, 4H). LCMS (APCI+) m/z 214 [M+H]+; Rt=1.60 min.

Workup

  1. customfor 3 days
  2. customThe catalyst was removed by filtration
  3. customThe filtrate was evaporated under vacuum
  4. customThe resulting residue was purified by column chromatography (DCM:MeOH, 20:1 to DCM:MeOH:Et3N, 100:10:1)

Sources & evidence

ORD record
ord-e3b328e1545e4f8580bc046a78187e93
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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