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

HRID 1971030

反応式

HRID 1971030 の反応式
[C:1](=O)([O:34]CCC(C)C)[O:2][CH2:3][N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][N:22]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])C=4Cl)[CH2:21][CH2:20]3)[CH:12]=2)[CH2:7][CH2:6][C:5]1=[O:33].[C:41]([Cl:44])(Cl)=O.CC(C)CCO.ClC1C(Cl)=CC=CC=1N1CCN(CCCCO[C:70]2[CH:79]=[C:78]3[C:73]([CH2:74]CC(=O)N3CO)=[CH:72][CH:71]=2)CC1.C([N:85](CC)CC)C>O1CCCC1.CN(C)C1C=CN=CC=1.ClCCl.C(OCC)(=O)C.N1C=CC=CC=1>[CH2:74]([NH:85][C:1](=[O:34])[O:2][CH2:3][N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][N:22]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:41]=4[Cl:44])[CH2:21][CH2:20]3)[CH:12]=2)[CH2:7][CH2:6][C:5]1=[O:33])[C:73]1[CH:78]=[CH:79][CH:70]=[CH:71][CH:72]=1

参加物

11

反応物 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 31260Isoamyl AlcoholHCID 50906166(7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl isopentyl carbonate2 回HCID 58096483N-Hydroxymethyl aripiprazole

生成物 1

HCID 49854811(7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl benzylcarbamate収率 55%

試薬・触媒・溶媒 5

HCID 142844-(Dimethylamino)pyridine触媒HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

(7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinolin-1(2H)-yl)methyl isopentyl carbonate (Example 10: Compound 84) To a solution of phosgene (20% in toluene, 54 mL, 110 mmol) in tetrahydrofuran (100 mL) was added a solution of 3-methyl-1-butanol (1.7 mL, 15.7 mmol) in tetrahydrofuran (50 mL) over 1 hour. After 4 hours the volatiles were removed under vacuum and the residue added to a solution of the hemi-aminal A1 (3 g, 4.7 mmol), 4-dimethylaminopyridine (0.3 g, 1.9 mmol), pyridine (10 mL) and triethylamine (1.3 mL, 9.4 mmol) in dichloromethane (30 mL). After being stirred for 72 hours, the reaction mixture was diluted with ethyl acetate (100 mL) and washed with 5% aqueous NaHCO3/brine (1:1, 100 mL). The organic phase was dried over MgSO4, filtered and evaporated under vacuum. The residue was further purified by chromatography on silica eluting with ethyl acetate/dichloromethane/methanol (1:1:0.1) to give the desired product as a yellow oil (1.54 g, 55% yield). 1H NMR (CDCl3, 300 MHz) δ 1.90-1.95 (m, 6H), 1.50-1.60 (m, 4H), 1.65-1.79 (m, 2H), 1.79-1.89 (m, 2H), 2.50 (t, 2H), 2.60-2.72 (m, 6H), 2.82-2.90 (m, 2H), 3.02-3.11 (m, 4H), 3.98 (t, 2H), 4.21 (t, 2H), 5.92 (s, 2H), 6.56 (dd, 1H), 6.67 (d, 1H), 6.95-7.00 (m, 1H), 7.05 (d, 1H), 7.13-7.19 (m, 2H); m/z (M+H) 592.48 and 594.46.

後処理

  1. customAfter 4 hours the volatiles were removed under vacuum
  2. washwashed with 5% aqueous NaHCO3/brine (1:1, 100 mL)
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated under vacuum
  6. customThe residue was further purified by chromatography on silica eluting with ethyl acetate/dichloromethane/methanol (1:1:0.1)

出典と根拠

ORDレコード
ord-e849617b5af64efeb1fe24272cf61315
出典データセット
uspto-grants-2013_04
特許番号
US08431576B2

関連ノート

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