Triethylamine → (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl 4-acetamidobutanoate

HRID 1971034Notes

Reaction equation

HRID 1971034 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:29]=[C:28]3[C:23]([CH2:24][CH2:25][C:26](=[O:32])[N:27]3[CH2:30][OH:31])=[CH:22][CH:21]=2)[CH2:11][CH2:10]1.C(N(CC)CC)C.CS(Cl)(=O)=O.[C:45]([NH:48][CH2:49][CH2:50][CH2:51][C:52](O)=[O:53])(=[O:47])[CH3:46]>ClCCl>[C:45]([NH:48][CH2:49][CH2:50][CH2:51][C:52]([O:31][CH2:30][N:27]1[C:28]2[C:23](=[CH:22][CH:21]=[C:20]([O:19][CH2:18][CH2:17][CH2:16][CH2:15][N:12]3[CH2:13][CH2:14][N:9]([C:3]4[CH:4]=[CH:5][CH:6]=[C:7]([Cl:8])[C:2]=4[Cl:1])[CH2:10][CH2:11]3)[CH:29]=2)[CH2:24][CH2:25][C:26]1=[O:32])=[O:53])(=[O:47])[CH3:46]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 181894-Acetamidobutyric acidHCID 31297Methanesulfonyl chlorideHCID 58096483N-Hydroxymethyl aripiprazole

Product 1

HCID 49853670(7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl 4-acetamidobutanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of hemiaminal A1 (2.6 g, 5.5 mmol) in dichloromethane (30 mL) was added triethylamine (2.3 mL, 16.4 mmol), followed by addition of methanesulfonyl chloride (0.47 g, 6.0 mmol) over 3 min. The reaction mixture was stirred for 25 min and then N-acetyl-4-aminobutyric acid (1.6 g, 10.1 mmol) added. The reaction mixture was then heated at reflux for 18 h, cooled and washed with sat. NaHCO3 (aq). The organic phase was dried over MgSO4, filtered and evaporated. The residue was further purified on silica eluting with 1:1:0.1 to 1:1:0.2 dichloromethane/ethyl acetate/methanol to give the title compound as an off white solid (1.1 g, 34%).

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux for 18 h
  3. temperaturecooled
  4. washwashed with sat. NaHCO3 (aq)
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was further purified on silica eluting with 1:1:0.1 to 1:1:0.2 dichloromethane/ethyl acetate/methanol

Sources & evidence

ORD record
ord-baf279eecaf445b284489dd4fe961118
Source dataset
uspto-grants-2013_04
Patent number
US08431576B2

Reaction notes

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