1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(7-nitro-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide

HRID 571197노트

반응식

HRID 571197 반응식
[N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[N:11]([CH2:13][C:14]([OH:16])=[O:15])[CH:10]=[CH:9]2)([O-:3])=[O:2].C(Cl)CCl.[Cl:21][C:22]1[CH:23]=[N+:24]([O-:47])[CH:25]=[C:26]([Cl:46])[C:27]=1[CH2:28][C@@H:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]([F:40])[F:39])=[C:33]([O:41][CH2:42][CH:43]2[CH2:45][CH2:44]2)[CH:32]=1)O.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:21][C:22]1[CH:23]=[N+:24]([O-:47])[CH:25]=[C:26]([Cl:46])[C:27]=1[CH2:28][C@@H:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]([F:40])[F:39])=[C:33]([O:41][CH2:42][CH:43]2[CH2:45][CH2:44]2)[CH:32]=1)[O:15][C:14](=[O:16])[CH2:13][N:11]1[C:12]2[C:8](=[CH:7][CH:6]=[CH:5][C:4]=2[N+:1]([O-:3])=[O:2])[CH:9]=[CH:10]1

참가 물질

7

반응물 4

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 68424240(7-Nitroindol-1-yl)-acetic acidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

생성물 1

HCID 86681615(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(7-nitro-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide수율 20.2%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

A mixture of 2-(7-nitro-1H-indol-1-yl)acetic acid (0.15 g, 0.681 mmol), EDC (0.131 g, 0.681 mmol), DMAP (0.128 g, 1.048 mmol) and (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.220 g, 0.524 mmol) in dry DCM (15 ml) was stirred at room temperature for 16 hours. Aqueous 2N HCl was added, and the organic phase was separated and dried over sodium sulfate; the solvent was removed and the crude was triturated with MeOH. The precipitate was filtered, washed with MeOH and dried affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(7-nitro-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide (0.066 g, 0.106 mmol, 20% yield). MS/ESI+ 622.1 [MH]+; [αD]=−112.6, c=0.22, MeOH; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.44 (s, 2H), 8.00 (dd, 1H), 7.82 (dd, 1H), 7.52 (d, 1H), 7.22 (t, 1H), 7.16 (d, 1H), 7.05 (d, 1H), 6.92 (dd, 1H), 7.06 (t, 1H), 6.76 (d, 1H), 5.95 (dd, 1H), 5.30 (d, 1H), 5.17 (d, 1H), 3.90 (d, 2H), 3.33-3.54 (m, 1H), 3.18 (dd, 1H), 0.99-1.39 (m, 1H), 0.48-0.72 (m, 2H), 0.36 (q, 2H).

후처리

  1. customthe organic phase was separated
  2. dry with materialdried over sodium sulfate
  3. customthe solvent was removed
  4. customthe crude was triturated with MeOH
  5. filtrationThe precipitate was filtered
  6. washwashed with MeOH
  7. customdried

출처 및 근거

ORD 기록
ord-e3a7c0d3580a49ff8faad0a3460e60bd
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09024027B2

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