Imidazole → HCID 25235915, compound

HRID 453050Notes

Reaction equation

HRID 453050 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([CH2:11][NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:24]=[CH:23]N=C1.C(Cl)(=O)C.Cl.[NH2:30][CH:31]1[CH2:36][CH2:35][C:34](=[O:37])[NH:33][C:32]1=[O:38].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C>[C:16]([O:15][C:13](=[O:14])[NH:12][CH2:11][C:9]1[CH:10]=[C:2]2[C:3]([C:4](=[O:6])[N:30]([CH:31]3[CH2:36][CH2:35][C:34](=[O:37])[NH:33][C:32]3=[O:38])[C:23]([CH3:24])=[N:1]2)=[CH:7][CH:8]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 68732363HCID 68732363, compound

Product 1

HCID 25235915HCID 25235915, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 2-amino-4-(tert-butoxycarbonylamino-methyl)-benzoic acid (24.75 g, 92.94 mmol), imidazole (7.59 g, 111.53 mmol) in acetonitrile (300 mL), was added acetyl chloride (7.96 mL, 111.53 mmol), and the mixture was stirred at room temperature overnight. To the mixture, was added 3-amino-piperidine-2,6-dione hydrogen chloride (15.30 g, 92.94 mmol), imidazole (12.66 g, 185.89 mmol) and triphenyl phosphite (29.23 mL, 111.53 mmol), and the mixture was heated to reflux for 6 hours. The mixture was cooled to room temperature and the brown mixture was filtered. The filtrate was evaporated and then purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give [3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-7-ylmethyl]-carbamic acid tert-butyl ester as a light yellow solid (24.57 g, 66% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, grad. to 95/5 in 5 min, kept 5 min, 5.97 min (99.7%); mp, 240-242° C.; 1HNMR (DMSO-d6) 1.29 (brs, 1H, CH from the BOC group), 1.40 (s, 8H, 8CH from the BOC group), 2.11-2.19 (m, 1H, CHH), 2.56-2.91 (m, 6H, CHCH2, CH3), 4.26 (d, J=6 Hz, 2H, CH2NH), 5.25 (dd, J=5, 11 Hz, 1H, CH), 7.35-7.99 (m, 4H, Ar and NHCH2), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.97, 23.49, 28.19, 30.60, 43.22, 56.48, 78.00, 118.84, 123.99, 125.41, 126.00, 146.93, 147.55, 155.15, 155.81, 160.29, 169.51, 172.61. LCMS MH=401; Anal Calcd For C20H24N4O5: C, 59.99; H, 6.04; N, 13.99. Found: C, 59.78; H, 5.78; N, 13.85.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 6 hours
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationthe brown mixture was filtered
  5. customThe filtrate was evaporated
  6. custompurified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%)

Sources & evidence

ORD record
ord-eec39a3ca27e42319af3e254f882d5e5
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

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