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 571197ノート

反応式

HRID 571197 の反応式
[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

参加物

7

反応物 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

生成物 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-oxide収率 20.2%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-e3a7c0d3580a49ff8faad0a3460e60bd
出典データセット
uspto-grants-2015_05
特許番号
US09024027B2

反応ノート

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