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

HRID 1971030

반응식

HRID 1971030 반응식
[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

참가 물질

11

반응물 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 31260Isoamyl AlcoholHCID 50906166HCID 50906166, 화합물2회HCID 58096483N-Hydroxymethyl aripiprazole

생성물 1

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

시약·촉매·용매 5

HCID 142844-(Dimethylamino)pyridine촉매HCID 1049Pyridine용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

(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.

후처리

  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)

출처 및 근거

ORD 기록
ord-e849617b5af64efeb1fe24272cf61315
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431576B2

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