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 571197Notes

Reaction equation

HRID 571197 reaction equation
[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

Participants

7

Reactant 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

Product 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-oxideYield 20.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e3a7c0d3580a49ff8faad0a3460e60bd
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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