1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(6-(trifluoromethyl)-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide

HRID 571194노트

반응식

HRID 571194 반응식
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[CH:8][N:9]2[CH2:12][C:13]([OH:15])=[O:14])=[CH:5][CH:4]=1.[Cl:18][C:19]1[CH:20]=[N+:21]([O-:44])[CH:22]=[C:23]([Cl:43])[C:24]=1[CH2:25][C@@H:26]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:37])[F:36])=[C:30]([O:38][CH2:39][CH:40]2[CH2:42][CH2:41]2)[CH:29]=1)O.C(Cl)CCl.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:18][C:19]1[CH:20]=[N+:21]([O-:44])[CH:22]=[C:23]([Cl:43])[C:24]=1[CH2:25][C@@H:26]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:37])[F:36])=[C:30]([O:38][CH2:39][CH:40]2[CH2:42][CH2:41]2)[CH:29]=1)[O:14][C:13](=[O:15])[CH2:12][N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([C:2]([F:16])([F:1])[F:17])[CH:11]=2)[CH:7]=[CH:8]1

참가 물질

7

반응물 4

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 670827152-(6-(trifluoromethyl)-1H-indol-1-yl)acetic acidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

생성물 1

HCID 86681613(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(6-(trifluoromethyl)-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide수율 48%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

A mixture of 2-(6-(trifluoromethyl)-1H-indol-1-yl)acetic acid (90 mg, 0.370 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (130 mg, 0.308 mmol), EDC (83 mg, 0.432 mmol) and DMAP (75 mg, 0.617 mmol) in dry DCM (5 ml) was stirred at room temperature overnight. Aqueous 1N HCl was added to the reaction mixture and the organic phase was separated, washed with brine and dried over sodium sulfate. The solvent was removed under vacuum, and the crude was purified by flash chromatography on silica gel column (DCM/MeOH 96/4) to give (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(6-(trifluoromethyl)-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide (95 mg, 0.147 mmol, 48% yield). MS/ESI+ 645.03 [MH]+; [αD]=−2.157, c=0.510; DCM; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.45 (s, 2H), 7.67-7.85 (m, 2H), 7.51 (d, 1H), 7.32 (dd, 1H), 7.12 (d, 1H), 6.97 (d, 1H), 6.87 (dd, 1H), 7.03 (t, 1H), 6.61 (dd, 1H), 5.98 (dd, 1H), 5.38 (d, 1H), 5.25 (d, 1H), 3.82 (d, 2H), 3.39 (dd, 1H), 3.19 (dd, 1H), 1.10-1.22 (m, 1H), 0.46-0.70 (m, 2H), 0.15-0.46 (m, 2H)

후처리

  1. customthe organic phase was separated
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed under vacuum
  5. customthe crude was purified by flash chromatography on silica gel column (DCM/MeOH 96/4)

출처 및 근거

ORD 기록
ord-8764e6e1786146f7aaa8aa42be780778
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09024027B2

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