4-Methylbenzaldehyde → [3-(3-Benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-3-(4-methyl-benzylamino)-propyl]-carbamic acid tert-butyl ester

HRID 1348805Notes

Reaction equation

HRID 1348805 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][CH2:8][CH2:9][CH:10]([NH2:30])[C:11]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:19](=[O:28])[C:18]2[C:13](=[CH:14][C:15]([Cl:29])=[CH:16][CH:17]=2)[N:12]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[C:41]1([CH3:49])[CH:46]=[CH:45][C:44]([CH:47]=O)=[CH:43][CH:42]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:31])[NH:7][CH2:8][CH2:9][CH:10]([C:11]1[N:20]([CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:19](=[O:28])[C:18]2[C:13](=[CH:14][C:15]([Cl:29])=[CH:16][CH:17]=2)[N:12]=1)[NH:30][CH2:49][C:41]1[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 77254-MethylbenzaldehydeHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 69226423[3-Amino-3-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-propyl]-carbamic acid tert-butyl ester

Product 1

HCID 69178479[3-(3-Benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-3-(4-methyl-benzylamino)-propyl]-carbamic acid tert-butyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Formula 107 where R1, R2, R4, R6, R7, R8 and R9 are H: R3 is Chloro; R5 is Benzyl; and R10 is p-Methyl-benzyl: To a solution of [3-amino-3-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-propyl]-carbamic acid tert-butyl ester (700 mg, 1.58 mmol) and DIEA (275 μL, 2.37 mmol) in 50 mL of DCM was added p-tolualdehyde (188 μL, 1.58 mmol). The mixture was stirred for 1 hour, after which sodium triacetoxyborohydride (500 mg, 2.37 mmol) was added. After stirring an additional 3 hours, the mixture was washed with saturated sodium bicarbonate solution, dried over sodium sulfate. The solvents were evaporated to dryness and the residue was purified by flash silica gel chromatography (stepwise gradient 1:4, 1:2, 1:1, 2:1, 4:1 with ethyl acetate:hexanes as eluent) to give the corresponding, pure compound of Formula 107, [3-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-3-(4-methyl-benzylamino)-propyl]-carbamic acid tert-butyl ester (760 mg, 88%).

Workup

  1. stirringAfter stirring an additional 3 hours
  2. washthe mixture was washed with saturated sodium bicarbonate solution
  3. dry with materialdried over sodium sulfate
  4. customThe solvents were evaporated to dryness
  5. customthe residue was purified by flash silica gel chromatography (stepwise gradient 1:4, 1:2, 1:1, 2:1, 4:1 with ethyl acetate

Sources & evidence

ORD record
ord-0f4dafbc8a274237bd4c99d8c2a21447
Source dataset
uspto-grants-2007_05
Patent number
US07211580B2

Reaction notes

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