Cyclohexanecarboxylic acid → N-[1-(cyclohexylcarbonyl)piperidin-4-yl]-4-phenylquinazolin-2-amine

HRID 1515181Notes

Reaction equation

HRID 1515181 reaction equation
[C:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]([NH:17][CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:24]1([C:30](O)=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OOC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[Cl-].[Li+]>CN(C)C=O>[CH:24]1([C:30]([N:21]2[CH2:22][CH2:23][CH:18]([NH:17][C:9]3[N:8]=[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]=3)[CH2:19][CH2:20]2)=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

7

Reactant 5

HCID 7413Cyclohexanecarboxylic acidHCID 8471TriethylamineHCID 433294Lithium ChlorideHCID 441404384-phenyl-N-(piperidine-4-yl)quinazolin-2-amineHCID 86629759O-(7-azabenzotriazol-1-yloxy)-N,N,N',N'-tetramethyluronium hexafluorophosphate

Product 1

HCID 44138291N-[1-(cyclohexylcarbonyl)piperidin-4-yl]-4-phenylquinazolin-2-amineYield 77.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-phenyl-N-(piperidine-4-yl)quinazolin-2-amine (0.34 g, 1.0 mmol), cyclohexanecarboxylic acid (0.15 g, 1.2 mmol), and triethylamine (1.38 mL, 10 mmol) in dimethylformamide (15 mL) was added O-(7-azabenzotriazol-1-yloxy)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 0.57 g, 1.5 mmol) and the solution was stirred at rt for 16 h. An aqueous 5% solution of lithium chloride (100 mL) was added and the resulting solid was filtered and recrystallized in methanol/methyl-tert-butyl ether to yield N-[1-(cyclohexylcarbonyl)piperidin-4-yl]-4-phenylquinazolin-2-amine (0.32 g, 77%) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 11.81 (d, 1H), 7.70-7.65 (m, 4H), 7.56-7.53 (m, 3H), 7.21-7.16 (m, 1H), 5.26 (d, 1H), 4.52 (m, 1H), 4.34-4.28 (m, 1H), 3.92 (m, 1H), 3.28 (t, 1H), 2.94 (t, 1H), 2.51 (tt, 2H), 2.29-2.16 (m, 2H), 1.83-1.69 (m, 5H), 1.57-1.44 (m, 4H), 1.30-1.26 (m, 2H). MS (EI) for C26H30N4O: 415.3 (MH+).

Workup

  1. filtrationthe resulting solid was filtered
  2. customrecrystallized in methanol/methyl-tert-butyl ether

Sources & evidence

ORD record
ord-9c8c9ca2b02343e28881bc75eefe1501
Source dataset
uspto-grants-2012_07
Patent number
US08222263B2

Reaction notes

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