1,2-Dichloroethane → N-[(1R)-1-(5-Fluoro-1-oxidopyridin-2-yl)ethyl]-3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzamide

HRID 1257546노트

반응식

HRID 1257546 반응식
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]([CH:14]=[C:15]([C:17]3[CH2:21][C@@H:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[O:19][N:18]=3)[CH:16]=2)[C:11](O)=[O:12])=[N:6][CH:7]=1.Cl.[F:29][C:30]1[CH:31]=[CH:32][C:33]([C@H:37]([NH2:39])[CH3:38])=[N+:34]([O-:36])[CH:35]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C)C=O>[F:29][C:30]1[CH:31]=[CH:32][C:33]([C@H:37]([NH:39][C:11](=[O:12])[C:10]2[CH:14]=[C:15]([C:17]3[CH2:21][C@@H:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)[O:19][N:18]=3)[CH:16]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=3)[CH:9]=2)[CH3:38])=[N+:34]([O-:36])[CH:35]=1

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 66894903HCID 66894903, 화합물HCID 66895339(1R)-1-(5-fluoro-1-oxidopyridin-2-yl)ethanamine hydrochloride salt

생성물 1

HCID 42634194N-[(1R)-1-(5-Fluoro-1-oxidopyridin-2-yl)ethyl]-3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzamide수율 77%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoic acid (50.0 mg, 0.12 mmol) in N,N-dimethylformamide (1 mL) were added (1R)-1-(5-fluoro-1-oxidopyridin-2-yl)ethanamine hydrochloride salt (33.4 mg, 0.17 mmol), EDC (33.3 mg, 0.17 mmol), HOAT (7.9 mg, 0.06 mmol) and triethylamine (0.11 mL, 0.81 mmol). The reaction mixture was stirred at ambient temperature for 1.5 h. The reaction mixture was heated to 50° C. After 20 min, the mixture was cooled to ambient temperature and the solid in the reaction was filtered off. Purification by reverse phase chromatography (C-18, 95% water/acetonitrile→65% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (46 mg). HRMS 498.1954 (M+1). 1H NMR (400 MHz, CDCl3): δ 8.56 (d, J=4.8 Hz, 1H); 8.48 (s, 1H); 8.46-8.35 (m, 3H); 8.15-8.08 (m, 2H); 7.73-7.65 (m, 2H); 7.54 (t, J=8.9 Hz, 2H); 7.34 (t, J=7.8 Hz, 1H); 7.20 (dd, J=7.7, 4.8 Hz, 1H); 7.06 (ddd, J=8.8, 6.6, 2.4 Hz, 1H); 5.86 (dd, J=10.9, 6.9 Hz, 1H); 5.58-5.48 (m, 1H); 3.92-3.74 (m, 2H); 2.35 (s, 3H); 1.70 (d, J=7.0 Hz, 3H).

후처리

  1. temperatureThe reaction mixture was heated to 50° C
  2. waitAfter 20 min
  3. temperaturethe mixture was cooled to ambient temperature
  4. filtrationthe solid in the reaction was filtered off
  5. customPurification by reverse phase chromatography (C-18, 95% water/acetonitrile→65% water/acetonitrile with 0.1% trifluoroacetic acid)

출처 및 근거

ORD 기록
ord-bd098c8a8de348a79dc52185bea56691
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461185B2

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