1,2-Dichloroethane → HCID 86681756, compound

HRID 571339Notes

Reaction equation

HRID 571339 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[OH:10].[CH3:28][S:29]([NH:32][CH2:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[C:39](=[O:43])[N:38]([CH2:44][C:45](O)=[O:46])[C:37]2=[O:48])(=[O:31])=[O:30].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[O:10][C:45](=[O:46])[CH2:44][N:38]1[C:37](=[O:48])[C:36]2[C:40](=[CH:41][CH:42]=[C:34]([CH2:33][NH:32][S:29]([CH3:28])(=[O:31])=[O:30])[CH:35]=2)[C:39]1=[O:43]

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 86681755HCID 86681755, compound

Product 1

HCID 86681756HCID 86681756, compoundYield 30.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.229 g, 0.544 mmol), 2-(5-(methylsulfonamidomethyl)-1,3-dioxoisoindolin-2-yl)acetic acid (0.170 g, 0.544 mmol), EDC (0.313 g, 1.633 mmol) and DMAP (0.133 g, 1.089 mmol) were dissolved in DCM (20 ml), and the solution was stirred at room temperature for 20 hours. The mixture was diluted with DCM and washed with 0.5N HCl, aqueous 5% NaHCO3 and brine. The organic phase was dried over sodium sulfate, and the solvent removed under vacuum. The crude was purified by preparative HPLC (Method 1) to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(methylsulfonamido methyl)-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (0.120 g, 0.168 mmol, 30.9% yield, MS/ESI+ 714.06 [MH]+, [aD]=−27.89, c=0.9, DCM; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.44 (s, 2H), 7.88-7.94 (m, 2H), 7.85 (dd, 1H), 7.77 (t, 1H), 7.19 (d, 1H), 7.08 (s, 1H), 6.96 (dd, 1H), 7.08 (t, 1H), 6.01 (dd, 1H), 4.42 (s, 2H), 4.23-4.56 (m, 2H), 3.83-4.00 (m, 2H), 3.39 (dd, 1H), 3.22 (dd, 1H), 2.95 (s, 3H), 1.10-1.34 (m, 1H), 0.49-0.67 (m, 2H), 0.30-0.46 (m, 2H)

Workup

  1. washwashed with 0.5N HCl, aqueous 5% NaHCO3 and brine
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. customthe solvent removed under vacuum
  4. customThe crude was purified by preparative HPLC (Method 1)

Sources & evidence

ORD record
ord-7b35dcc45350413db8eb7ecee3f31e2f
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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