4-Methylmorpholine → HCID 67281838, compound

HRID 1616138Notes

Reaction equation

HRID 1616138 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]2[C:8]([C:9](=[O:18])[NH:10][CH:11]([C:15]([OH:17])=O)[NH:12]2)=[CH:7][CH:6]=1)=[O:4].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:48][CH:49]1[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:51][CH2:50]1>O.CN(C=O)C>[C:58]([O:57][C:55]([N:52]1[CH2:53][CH2:54][CH:49]([NH:48][C:15]([CH:11]2[NH:10][C:9](=[O:18])[C:8]3[C:13](=[CH:14][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=3)[NH:12]2)=[O:17])[CH2:50][CH2:51]1)=[O:56])([CH3:61])([CH3:59])[CH3:60]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 12682914-Amino-1-Boc-piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67282748HCID 67282748, compound

Product 1

HCID 67281838HCID 67281838, compoundYield 23.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 7-(methoxycarbonyl)-4-oxo-1,2,3,4-tetrahydroquinazoline-2-carboxylic acid (0.15 g, 0.6 mmol), DMF (8 mL), N-methylmorpholine (66 μL, 0.6 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.23 g, 1.2 mmol) and 1-hydroxybenzotriazole (81 mg, 0.6 mmol) was stirred for 15 min and 4-amino-1-Boc-piperidine (144 mg, 0.72 mmol) was added. The reaction mixture was stirred at rt for 1 d. Water was added and the mixture was extracted with EtOAc (2×). The combined organic phases were then washed with water, and brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash silica gel chromatography (0% to 100% EtOAc/DCM) to afford to afford methyl 2-({[1-(tert-butoxycarbonyl)piperidin-4-yl]amino}carbonyl)-4-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate (60 mg, 20%). LC-MS: (FA) ES+ 333.

Workup

  1. stirringThe reaction mixture was stirred at rt for 1 d
  2. extractionthe mixture was extracted with EtOAc (2×)
  3. washThe combined organic phases were then washed with water, and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash silica gel chromatography (0% to 100% EtOAc/DCM)
  8. customto afford

Sources & evidence

ORD record
ord-f766cad1ad2d4756939ca81faa6d3e0e
Source dataset
uspto-grants-2014_07
Patent number
US08765773B2

Reaction notes

Loading…