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Triethylamine → 2-{(R)-1-[N-Toluoyl-(3-Phthalimido-2-oxo-propyl)amino]-2-methyl-propyl}-3-benzyl-7-chloro-3H-quinazolin-4-one

HRID 1350634
Notes
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Reaction equation

HRID 1350634 reaction equation
[C:1]1(=[O:39])[N:5]([CH2:6][C:7](=[O:33])[CH2:8][NH:9][C@@H:10]([C:14]2[N:23]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:22](=[O:31])[C:21]3[C:16](=[CH:17][C:18]([Cl:32])=[CH:19][CH:20]=3)[N:15]=2)[CH:11]([CH3:13])[CH3:12])[C:4](=[O:34])[C:3]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:2]12.CCN(CC)CC.[C:47]1([CH3:56])[C:48]([C:53](Cl)=[O:54])=[CH:49][CH:50]=[CH:51][CH:52]=1>C(Cl)Cl>[C:47]1([CH3:56])[C:48]([C:53]([N:9]([CH2:8][C:7](=[O:33])[CH2:6][N:5]2[C:4](=[O:34])[C:3]3=[CH:35][CH:36]=[CH:37][CH:38]=[C:2]3[C:1]2=[O:39])[C@@H:10]([C:14]2[N:23]([CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:22](=[O:31])[C:21]3[C:16](=[CH:17][C:18]([Cl:32])=[CH:19][CH:20]=3)[N:15]=2)[CH:11]([CH3:13])[CH3:12])=[O:54])=[CH:49][CH:50]=[CH:51][CH:52]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 702762-Methylbenzoyl chlorideHCID 690735002-[(R)-1-(3-Phthalimido-2-oxo-propylamino)-2-methyl-propyl]-3-benzyl-7-chloro-3H-quinazolin-4-one

Product 1

HCID 690781822-{(R)-1-[N-Toluoyl-(3-Phthalimido-2-oxo-propyl)amino]-2-methyl-propyl}-3-benzyl-7-chloro-3H-quinazolin-4-oneYield 73%

Reagents, catalysts & solvents 1

HCID 6344
Dichloromethane
Solvent

Procedure

To 2-[(R)-1-(3-phthalimido-2-oxo-propylamino)-2-methyl-propyl]-3-benzyl-7-chloro-3H-quinazolin-4-one (7.22 g, 13.3 mMol) in CH2Cl2 (50 mL) was added Et3N (2.0 mL, 14.3 mMol) and toluoyl chloride (1.9 mL, 14.4 mMol). The reaction was stirred at RT for 18 h, concentrated under vacuum, taken up in EtOAc, washed with 1 N HCl, brine, dried (MgSO4) and evaporated to dryness. Purification by flash chromatography on silica gel (1% MeOH/CH2Cl2) followed by trituration with (1:1) Et2O/pet. ether, filtration and drying under vacuum gave the title compound (6.41 g, 73%) as a white solid. A side fraction (1.20 g) which contained mostly product was also obtained: 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J=8.6 Hz, 1H), 7.69–7.78 (m, 5H), 7.45–7.49 (m, 3H), 7.34 (t, 2H), 7.25–7.29 (m, 3H), 7.15 (d, J=8.1 Hz, 2H), 6.19 (d, J=15.9 Hz, 1H), 5.82 (d, J=10.6 Hz, 1H), 5.12 (d, J=15.9 Hz, 1H), 4.56 (d, J=18.8 Hz, 1H), 4.26 (d, J=18.8 Hz, 1H), 4.09 (d, J=17.6 Hz, 1H), 3.90 (d, J=17.6 Hz, 1H), 2.62 (m, 1H), 2.42 (s, 3H), 0.93 (d, J=6.8 Hz, 3H), 0.32 (d, J=6.4 Hz, 3H); MS (ES) m/e 661.2 (M+H)+.

Workup

  1. concentrationconcentrated under vacuum
  2. washwashed with 1 N HCl, brine
  3. dry with materialdried (MgSO4)
  4. customevaporated to dryness
  5. customPurification by flash chromatography on silica gel (1% MeOH/CH2Cl2)
  6. filtrationfollowed by trituration with (1:1) Et2O/pet. ether, filtration
  7. customdrying under vacuum

Sources & evidence

ORD record
ord-8b391e4daeb24580ac9fcbafddf8b658
Source dataset
uspto-grants-2007_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07214800B2

Reaction notes

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