1,2-Dichloroethane → HCID 86681668, compound

HRID 571254Notes

Reaction equation

HRID 571254 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][C:16]([OH:18])=[O:17])[CH2:10][CH2:9]2)(=[O:4])=[O:3].[Cl:19][C:20]1[CH:21]=[N+:22]([O-:45])[CH:23]=[C:24]([Cl:44])[C:25]=1[CH2:26][C@@H:27]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH:36]([F:38])[F:37])=[C:31]([O:39][CH2:40][CH:41]2[CH2:43][CH2:42]2)[CH:30]=1)O.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:19][C:20]1[CH:21]=[N+:22]([O-:45])[CH:23]=[C:24]([Cl:44])[C:25]=1[CH2:26][C@@H:27]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH:36]([F:38])[F:37])=[C:31]([O:39][CH2:40][CH:41]2[CH2:43][CH2:42]2)[CH:30]=1)[O:17][C:16](=[O:18])[CH2:15][N:11]1[C:12]2[C:8](=[CH:7][C:6]([NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[CH:14][CH:13]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 86681666HCID 86681666, compound2×

Product 1

HCID 86681668HCID 86681668, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(5-(methylsulfonamido)indolin-1-yl)acetic acid (0.154 g, 0.571 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.200 g, 0.476 mmol), EDC (0.128 g, 0.666 mmol) and DMAP (0.116 g, 0.952 mmol) in dry DCM (10 ml) was stirred at room temperature for 2.5 hours. Additional 2-(5-(methylsulfonamido)indolin-1-yl)acetic acid (0.072 g, 0.267 mmol) was added, and the mixture was stirred overnight at room temperature. The solvent was removed and the crude was purified by flash chromatography on silica gel column (DCM:MeOH=98:2). A further purification by preparative HPLC (Method 1) under neutral conditions was required to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(methylsulfonamido)indolin-1-yl)acetoxy)ethyl)-pyridine 1-oxide (0.0817 g, 0.121 mmol, 26% yield). MS/ESI+ 672.05 [MH]+; [αD]=+10.81, c=0.518; DCM; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.84 (br. s., 1H), 8.55 (s, 2H), 7.17 (d, 1H), 7.08 (d, 1H), 6.94 (dd, 1H), 6.92 (d, 1H), 7.06 (t, 1H), 6.81 (dd, 1H), 6.22 (d, 1H), 6.03 (dd, 1H), 4.10 (d, 1H), 3.90 (d, 2H), 3.92 (d, 1H), 3.43 (dd, 1H), 3.32-3.39 (m, 2H), 3.22 (dd, 1H), 2.89 (t, 2H), 2.83 (s, 3H), 1.08-1.31 (m, 1H), 0.49-0.68 (m, 2H), 0.18-0.46 (m, 2H).

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. customThe solvent was removed
  3. customthe crude was purified by flash chromatography on silica gel column (DCM:MeOH=98:2)
  4. customA further purification by preparative HPLC (Method 1) under neutral conditions

Sources & evidence

ORD record
ord-41208736a91644cb929bfbc73e23c4b7
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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