1,1'-Carbonyldiimidazole → 3-(1-Benzylpiperidin-4-yl)-7-fluoro-3,4-dihydroquinazolin-2(1H)-one

HRID 501987Notes

Reaction equation

HRID 501987 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][C:14]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:15]=1[CH2:16][NH:17][CH:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:20][CH2:19]1>O1CCCC1>[CH2:24]([N:21]1[CH2:22][CH2:23][CH:18]([N:17]2[CH2:16][C:15]3[C:14](=[CH:34][C:33]([F:35])=[CH:32][CH:31]=3)[NH:13][C:1]2=[O:2])[CH2:19][CH2:20]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 59424361N-(2-amino-4-fluorobenzyl)-1-benzylpiperidin-4-amine

Product 1

HCID 594243183-(1-Benzylpiperidin-4-yl)-7-fluoro-3,4-dihydroquinazolin-2(1H)-oneYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1′-Carbonyldiimidazole (6.92 g, 42.7 mmol) was added to a solution of N-(2-amino-4-fluorobenzyl)-1-benzylpiperidin-4-amine (8.64 g, 30.2 mmol) in dry tetrahydrofuran (150 mL) at 0° C. in one portion. After 5 min, the mixture was allowed to warm to room temperature and stirred for 3 h. The reaction was partitioned between water/diethyl ether (200 mL/200 mL). After separation, the aqueous solution was extracted with diethyl ether (200 mL). The combined organic solution was washed with brine (100 mL), dried over magnesium sulfate, and concentrated in vacuo to afford a light yellow solid which was triturated with diethyl ether (3×10 mL) to give the title compound as a white solid (3.41 g, 36% yield). 1H-NMR (CDCl3, 400 MHz) δ 7.40-7.18 (m, 5H), 6.92-6.82 (m, 1H), 6.75 (dd, J=8.2, 2.6, 1H), 6.66 (dd, J=8.8, 4.8, 1H), 4.48-4.34 (m, 1H), 4.03 (s, 2H), 3.53 (s, 2H), 2.98 (d, J=11.2, 2H), 2.37-2.12 (m, 2H), 1.99-1.82 (m, 2H), 1.67 (d, J=11.2, 2H); Mass spec.: 340.03 (MH+).

Workup

  1. customThe reaction was partitioned between water/diethyl ether (200 mL/200 mL)
  2. customAfter separation
  3. extractionthe aqueous solution was extracted with diethyl ether (200 mL)
  4. washThe combined organic solution was washed with brine (100 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto afford a light yellow solid which
  8. customwas triturated with diethyl ether (3×10 mL)

Sources & evidence

ORD record
ord-0debe7a0fb024d9699d7160298d435ed
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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