4-Methylbenzaldehyde → HCID 9889643, compound

HRID 225770Notes

Reaction equation

HRID 225770 reaction equation
[CH2:1]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][C:13]([Cl:19])=[CH:14][CH:15]=2)[N:10]([C:20]([CH:22]2[CH2:26][CH2:25][CH2:24][NH:23]2)=O)C1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27]1([CH3:35])[CH:32]=[CH:31][C:30]([CH:33]=O)=[CH:29][CH:28]=1>ClCCl>[CH2:1]([N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][C:13]([Cl:19])=[CH:14][CH:15]=2)[N:10]=[C:20]1[CH:22]1[CH2:26][CH2:25][CH2:24][N:23]1[CH2:33][C:30]1[CH:31]=[CH:32][C:27]([CH3:35])=[CH:28][CH:29]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 77254-MethylbenzaldehydeHCID 69066251HCID 69066251, compound

Product 1

HCID 9889643HCID 9889643, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Formula I where U—V is —N(R6)—CReRf—; R1, R2, R4, and Ra to Rf are H; R3 is chloro; R5 is benzyl: and R6 is p-methyl-benzyl: Crude 3-benzyl-7-chloro-1-(pyrrolidine-2-carbonyl)-2,3-dihydro-1H-quinazoline-4-one (170 mg, 0.50 mmol) dissolved in dichloromethane (5 mL) was treated with p-tolualdehyde (80 μL, 0.7 mmol) and NaHB(OAc)3 (350 mg, 1.65 mmol), and the mixture was stirred for 40 minutes at room temperature. The reaction was quenched with saturated NaHCO3 (2.2 mL) and the aqueous phase extracted with dichloromethane (25 mL). The organic layers were combined and dried over Na2SO3, filtered and concentrated under vacuum. The crude residue was purified by silica gel chromatography using a stepwise gradient of 20% ethyl acetate/hexanes to 50% methanol/ethyl acetate as eluent to give 52.5 mg (24% yield) of desired product of Formula I, 3-benzyl-7-chloro-2-[1-(4-methyl-benzyl)-pyrrolidin-2-yl]-3Hquinazolin4-one. LRMS (MH+) m/z 445.

Workup

  1. customThe reaction was quenched with saturated NaHCO3 (2.2 mL)
  2. extractionthe aqueous phase extracted with dichloromethane (25 mL)
  3. dry with materialdried over Na2SO3
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-80f68680a67b46a1bbc235f16d9a516e
Source dataset
uspto-grants-2009_07
Patent number
US07557115B2

Reaction notes

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