4-Methylbenzoyl Chloride → HCID 11377053, compound

HRID 1743324Notes

Reaction equation

HRID 1743324 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][CH2:8][CH2:9][CH2:10][NH:11][CH:12]([C:16]1[N:25]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:24](=[O:33])[C:23]2[C:18](=[CH:19][C:20]([Cl:34])=[CH:21][CH:22]=2)[N:17]=1)[CH:13]([CH3:15])[CH3:14])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[C:45]1([CH3:54])[CH:50]=[CH:49][C:48]([C:51](Cl)=[O:52])=[CH:47][CH:46]=1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:35])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([C@@H:12]([C:16]1[N:25]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:24](=[O:33])[C:23]2[C:18](=[CH:19][C:20]([Cl:34])=[CH:21][CH:22]=2)[N:17]=1)[CH:13]([CH3:15])[CH3:14])[C:51](=[O:52])[C:48]1[CH:49]=[CH:50][C:45]([CH3:54])=[CH:46][CH:47]=1)([CH3:3])([CH3:4])[CH3:2].[C:1]([O:5][C:6](=[O:35])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH:12]([C:16]1[N:25]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:24](=[O:33])[C:23]2[C:18](=[CH:19][C:20]([Cl:34])=[CH:21][CH:22]=2)[N:17]=1)[CH:13]([CH3:15])[CH3:14])[C:51](=[O:52])[C:48]1[CH:49]=[CH:50][C:45]([CH3:54])=[CH:46][CH:47]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 134054-Methylbenzoyl ChlorideHCID 81531DiisopropylethylamineHCID 53473333HCID 53473333, compound

Product 2

HCID 11377053HCID 11377053, compoundHCID 69518107HCID 69518107, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet and cold bath was charged with 16.0 g of {3-[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propylamino]-propyl}-carbamic acid tert-butyl ester (the compound of Formula 302 prepared, e.g., as described in Example 1.7 or 3.2), 80 mL of DCM and 9.1 g (12 mL)(2.2 eq) of DIPEA and stirred until dissolved. To the stirring solution, p-toluoyl chloride 5.5 g (4.7 mL)(1.1 eq) was added and stirring continued for approximately 6 hours until the reaction was determined to be completed by TLC (hexanes/ethyl acetate 1:1). The reaction was quenched with methanol (5 mL) and stirred for an additional 30 minutes, then cooled followed by addition of 1N hydrochloric acid (exothermic) to wash until acidic. The resulting solution was dried over sodium sulfate, the solvents stripped under vacuum at 30–40° C. The crude product thus obtained was purified on a silica gel column (eluted with 15% ethyl acetate in hexanes) and concentrated to give the title compound of Formula 304 {3-[[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propyl]-(4-methyl-benzoyl)-amino]-propyl}-carbamic acid tert-butyl ester as an off-white foam solid, 10.8 g (60% yield).

Workup

  1. customA dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, nitrogen inlet and cold bath
  2. customprepared
  3. dissolutionuntil dissolved
  4. stirringstirring
  5. customThe reaction was quenched with methanol (5 mL)
  6. stirringstirred for an additional 30 minutes
  7. temperaturecooled
  8. additionfollowed by addition of 1N hydrochloric acid (exothermic)
  9. washto wash until acidic
  10. dry with materialThe resulting solution was dried over sodium sulfate
  11. customstripped under vacuum at 30–40° C
  12. customThe crude product thus obtained
  13. customwas purified on a silica gel column (eluted with 15% ethyl acetate in hexanes)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-b0c3bfba0cd04c9b9299d690de65b83a
Source dataset
uspto-grants-2006_03
Patent number
US07009049B2

Reaction notes

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