Benzenesulfonyl chloride → 4-{2-Propanesulfonylamino-1-[4-(2-chloro-1-phenyl-ethoxy)-3-methoxy-phenyl]-ethylamino}-benzamidine

HRID 896742

반응식

HRID 896742 반응식
[CH2:1]([S:4](Cl)(=[O:6])=[O:5])[CH2:2][CH3:3].C1(S(Cl)(=O)=O)C=CC=CC=1.[NH2:18][CH2:19][CH:20]([NH:39][C:40]1[CH:47]=[CH:46][C:43]([C:44]#[N:45])=[CH:42][CH:41]=1)[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:29][Cl:30])=[C:23]([O:37][CH3:38])[CH:22]=1.C(OC1C(OC)=CC(C=O)=C([N+:66]([O-])=O)C=1)C1C=CC=CC=1.NC1C=CC(C#N)=CC=1.C([N+]#[C-])C1C=CC=CC=1.[B]>CO.O>[CH2:1]([S:4]([NH:18][CH2:19][CH:20]([NH:39][C:40]1[CH:41]=[CH:42][C:43]([C:44]([NH2:66])=[NH:45])=[CH:46][CH:47]=1)[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:29][Cl:30])=[C:23]([O:37][CH3:38])[CH:22]=1)(=[O:6])=[O:5])[CH2:2][CH3:3]

참가 물질

10

반응물 7

HCID 7369Benzenesulfonyl chlorideHCID 133964-AminobenzonitrileHCID 662791-Propanesulfonyl chlorideHCID 82558Benzyl isocyanideHCID 5613634-(Benzyloxy)-5-methoxy-2-nitrobenzaldehydeHCID 5462311BoronHCID 223512374-{2-Amino-1-[4-(2-chloro-1-phenyl-ethoxy)-3-methoxy-phenyl]-ethylamino}-benzonitrile

생성물 1

HCID 542004344-{2-Propanesulfonylamino-1-[4-(2-chloro-1-phenyl-ethoxy)-3-methoxy-phenyl]-ethylamino}-benzamidine

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

반응 조건

온도
60 °C

실험 절차

4-{2-propanesulfonylamino-1-[4-(2-chloro-1-phenyl-ethoxy)-3-methoxy-phenyl]-ethylamino}-benzamidine was prepared similarly to Example 2, except propanesulfonyl chloride was substituted for benzenesulfonyl chloride in the reaction with 4-{2-amino-1-[4-(2-chloro-1-phenyl-ethoxy)-3-methoxy-phenyl]-ethylamino}-benzonitrile. MS(M+H)=545. 4-Benzyloxy-5-methoxy-2-nitrobenzaldehyde (12.2 g 42 mmoles) and 4-aminobenzonitrile (5 g, 42 mmoles) were dissolved in methanol (165 ml) and stirred for two hours and then heated to 60° C. for 30 minutes. The reaction was allowed to cool to room temperature and benzyl isonitrile (5 g. 42 mmoles) added. The reaction was cooled to 0° C. and boron trifluoroetherate (16 ml, 126 mmoles) added dropwise over five minutes. The reaction was stirred at 0° C. for 20 minutes and then allowed to come to room temperature and then stirred at ambient temperature for two hours. Water (4 ml) was added and the mixture stirred at room temperature overnight. A yellow precipitate was evident the next morning and the solid filtered off. The solid was washed with methanol and air dried to yield 8 grams of the desired product. The solvent from the filtrate was removed in vacuo and replaced with ethyl acetate. The solution was washed with water and saturated sodium bicarbonate, dried over anhydrous magnesium sulfate and the solvent removed. The crude material was submitted to flash chromatography (hexanes: ethyl acetate, 1:1) to yield an additional 7 g of the desired product (4-Benzyloxy-5-methoxy-2-nitro-phenyl)-(4-cyano-phenylamino)-acetic acid methyl ester. 1HNMR(CDCl3): 7.68 (s, 1H), 7.4 (m, 7H), 7.0 (s, 1H), 6.61 (d, 2H), 6.2 (s, 1H), 5.2 (s,2H), 3.87 (s, 3H), 3.75 (s, 3H). (4-Benzyloxy-5-methoxy-2-nitro-phenyl)-(4-cyano-phenylamino)-acetic acid methyl ester (4.5 g, 10 mmole) was dissolved in dimethoxyethane and lithium borohydride (0.210 g, 10 mmole) added. The reaction was heated to reflux for three hours and cooled to room temperature. The reaction was quenched with water containing acetic acid and diluted with ethyl acetate. After transferring to a separatory funnel, the organic layer was washed with water several times. The organic layer was dried over anhydrous sodium sulfate, filtered and the solvent removed. The crude material was then submitted to flash chromatography to yield 3.1 g of 4-[1-(4-Benzyloxy-5-methoxy-2-nitro-phenyl)-2-hydroxy-ethylamino]-benzonitrile (74%).

후처리

  1. temperatureto cool to room temperature
  2. temperatureThe reaction was cooled to 0° C.
  3. stirringThe reaction was stirred at 0° C. for 20 minutes
  4. customto come to room temperature
  5. stirringstirred at ambient temperature for two hours
  6. stirringthe mixture stirred at room temperature overnight
  7. filtrationthe solid filtered off
  8. washThe solid was washed with methanol and air
  9. customdried

출처 및 근거

ORD 기록
ord-cd0165ef4e2646a790483f6a01b45d1b
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06919369B2

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