1,2-Dichloroethane → HCID 86593649, compound

HRID 1348806Notes

Reaction equation

HRID 1348806 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[CH2:12][CH2:11][CH2:10][CH:9]1[C:15]([NH:17][C:18]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:19]=1[C:20]([OH:22])=O)=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.[CH2:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CN(C=O)C>[CH2:32]([NH:39][C:20]([C:19]1[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:18]=1[NH:17][C:15]([CH:9]1[CH2:10][CH2:11][CH2:12][C:13](=[O:14])[N:8]1[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:16])=[O:22])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 7504BenzylamineHCID 21091651HCID 21091651, compound

Product 1

HCID 86593649HCID 86593649, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Formula I where R1, R2, R4, R6, R7, R8 and R9 are H; R3 is Chloro; R5 is Benzyl, R10 is Benzyl; and V is CR′R″ where R′ and R″ are H: To a solution of 2-[(1-benzyl-6-oxo-piperidine-2-carbonyl)-amino]-4-chloro-benzoic acid (165 mg, 0.427 mmol) in 5 mL of DMF was added EDC (245 mg, 1.28 mmol) and the mixture stirred at room temperature. After 1 hour, benzylamine (140 μL, 1.28 mmol) was added, and the reaction mixture was stirred at room temperature for an additional 3 hours. After evaporating the solvents, the residue was dissolved in 100 mL of DCM, and washed with saturated sodium bicarbonate and brine. The organic layer was dried over sodium sulfate and filtered. The solvent was removed to afford crude 1-benzyl-6-oxo-piperidine-2-carboxylic acid (2-benzylcarbamoyl-5-chloro-phenyl)-amide, a compound of Formula 402. This was dried under vacuum and then added to a mixture of 10 mL of ethylene glycol and sodium hydroxide (17 mg, 0.425 mmol), followed by stirring at 130° C. for two days with monitoring by LC-MS. The mixture was then poured into 100 mL of water. After extraction with DCM, the resulting crude product was purified over silica gel (stepwise gradient 1:4, 1:2, 1:1, 2:1, 4:1 with ethyl acetate:hexanes as eluent) to give the desired pure product of Formula I, 3-benzyl-2-(1-benzyl-6-oxo-piperidin-2-yl)-7-chloro-3H-quinazolin-4-one (20 mg, 10%).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for an additional 3 hours
  2. customAfter evaporating the solvents
  3. dissolutionthe residue was dissolved in 100 mL of DCM
  4. washwashed with saturated sodium bicarbonate and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed

Sources & evidence

ORD record
ord-3b5ecfca5f6d430b9f5a9831a5abb731
Source dataset
uspto-grants-2007_05
Patent number
US07211580B2

Reaction notes

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