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

HRID 1971029

반응식

HRID 1971029 반응식
[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.[CH2:40]([N:47]=[C:48]=[O:49])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>CN(C)C1C=CN=CC=1.ClCCl>[CH2:40]([NH:47][C:48](=[O:49])[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])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 76639Benzyl isocyanateHCID 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 benzylcarbamate

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

반응 조건

온도
35 °C

실험 절차

To a solution of hemi-aminal A1 from Example 1 (4 g, 8.4 mmol), 4-dimethylaminopyridine (0.15 g, 1.3 mmol) and triethylamine (1.1 mL, 7.5 mmol) in dichloromethane (30 mL) was added benzylisocyanate (1.03 mL, 8.3 mmol) and the reaction mixture stirred for 24 hours. The reaction mixture was then heated at 35° C. for 20 hours, cooled and washed with water/brine (1:1, 50 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 an off white foam (530 mg, 14% yield). 1H NMR (CDCl3, 300 MHz) δ 1.58-1.88 (m, 4H), 2.48 (t, 2H), 2.60-2.72 (m, 6H), 2.85 (m, 2H), 300-3.12 (m, 4H), 3.96 (t, 2H), 4.40 (d, 2H), 5.13 (NH), 5.96 (s, 2H), 6.58 (dd, 1H), 6.79 (d, 1H), 6.92-6.98 (m, 1H), 7.04 (d, 1H), 7.12-7.16 (m, 1H), 7.23-7.35 (m, 6H); m/z (M+H) 611.12 and 613.10.

후처리

  1. temperaturecooled
  2. washwashed with water/brine (1:1, 50 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-2a8e86d95a834ffba80e65dfb27eb9d1
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431576B2

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