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

HRID 490267Notes

Reaction equation

HRID 490267 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

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 6344DichloromethaneSolvent

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, 1 H), 7.69-7.78 (m, 5 H), 7.45-7.49 (m, 3 H), 7.34 (t, 2 H), 7.25-7.29 (m, 3 H), 7.15 (d, J=8.1 Hz, 2 H), 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, 1 H), 4.26 (d, J=18.8 Hz, 1 H), 4.09 (d, J=17.6 Hz, 1 H), 3.90 (d, J=17.6 Hz, 1H), 2.62 (n, 1 H), 2.42 (s, 3 H), 0.93 (d, J=6.8 Hz, 3 H), 0.32 (d, J=6.4 Hz, 3 H); 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-ec9b197d64de4da6ba5cda78b1f3739c
Source dataset
uspto-grants-2009_05
Patent number
US07528137B2

Reaction notes

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