4-Methylmorpholine → [3-(4-Methyl-benzyl)-4-oxo-4-(4-quinazolin-4-yl-piperazin-1-yl)-butyl]-carbamic acid tert-butyl ester

HRID 1192440Notes

Reaction equation

HRID 1192440 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH:11]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)[C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[N:51]1([C:57]2[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[N:60]=[CH:59][N:58]=2)[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH2:10][CH:11]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)[C:12](=[O:14])[N:54]1[CH2:55][CH2:56][N:51]([C:57]2[C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[N:60]=[CH:59][N:58]=2)[CH2:52][CH2:53]1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 18585334-Piperazin-1-ylquinazolineHCID 510720044-[(tert-Butoxycarbonyl)amino]-2-(4-methylbenzyl)-butanoic acid

Product 1

HCID 67540421[3-(4-Methyl-benzyl)-4-oxo-4-(4-quinazolin-4-yl-piperazin-1-yl)-butyl]-carbamic acid tert-butyl esterYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution containing 4-tert-Butoxycarbonylamino-2-(4-methylbenzyl)-butyric acid (0.24 g, 0.77 mmol) in 25 mL of DMF under a nitrogen atmosphere was added EDCI (0.16 g, 0.84 mmol), HOBT (130 mg, 0.84 mmol) and NMM (0.28 g, 2.8 mmol.) After stirring at room temperature for 15 minutes, 4-Piperazin-1-yl-quinazoline (200 mg, 0.93 mmol) was added and the reaction allowed to stir at room temperature. The reaction was diluted with ethyl acetate and washed with water, saturated sodium bicarbonate and water. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent and purification of the residue via biotage eluting with 10% MeOH/DCM gave [3-(4-Methyl-benzyl)-4-oxo-4-(4-quinazolin-4-yl-piperazin-1-yl)-butyl]-carbamic acid tert-butyl ester (0.225 g, 64%) as a white solid. LCMS (APCI+) m/z 504 [M+H]+; Rt: 3.03 min. 1H NMR (CDCl3, 400 MHz) δ 3.8.69 (1H, s), 7.92 (1H, d, J 8.3 Hz), 7.76-7.71 (2H, m), 7.45 (1H, t, J 7.8 Hz), 7.06 (4H, m), 4.53 (1H, br. s), 3.96-3.76 (2H, m), 3.63-3.54 (2H, m), 3.47-3.40 (2H, m), 3.24-2.84 (6H, m), 2.76-2.70 (1H, m), 2.27 (3H, s), 2.09-2.00 (1H, m), 1.73-1.65 (1H, m), 1.40 (9H, s.)

Workup

  1. stirringto stir at room temperature
  2. washwashed with water, saturated sodium bicarbonate and water
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationFiltration, removal of solvent and purification of the residue via biotage
  5. washeluting with 10% MeOH/DCM

Sources & evidence

ORD record
ord-d7748f55a52b4bbcb052f56fc551ed32
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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