1,2-Dichloroethane → HCID 86681758, compound

HRID 571341Notes

Reaction equation

HRID 571341 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].FC(F)(F)C(O)=O.[O:35]1[CH2:40][CH2:39][N:38]([CH2:41][CH2:42][N:43]([CH2:48][C:49]2[CH:50]=[C:51]3[C:55](=[CH:56][CH:57]=2)[C:54](=[O:58])[N:53]([CH2:59][C:60](O)=[O:61])[C:52]3=[O:63])[S:44]([CH3:47])(=[O:46])=[O:45])[CH2:37][CH2:36]1.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][CH: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:60](=[O:61])[CH2:59][N:53]1[C:52](=[O:63])[C:51]2[C:55](=[CH:56][CH:57]=[C:49]([CH2:48][N:43]([CH2:42][CH2:41][N:38]3[CH2:39][CH2:40][O:35][CH2:36][CH2:37]3)[S:44]([CH3:47])(=[O:46])=[O:45])[CH:50]=2)[C:54]1=[O:58]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687HCID 71092687, compoundHCID 86681759HCID 86681759, compound

Product 1

HCID 86681758HCID 86681758, compoundYield 36.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.174 g, 0.415 mmol), 2-(5-((N-(2-morpholinoethyl)methylsulfonamido)methyl)-1,3-dioxoisoindolin-2-yl)acetic acid 2,2,2 trifluoroacetic acid salt (0.224 g, 0.415 mmol), EDC (0.239 g, 1.246 mmol), and DMAP (0.101 g, 0.830 mmol) in DCM (10 ml) was stirred at room temperature for 3 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 filtration through a silica cartridge (DCM:MeOH=98:2); a further purification by flash chromatography on silica gel column (DCM:MeOH=99=1) was performed to afford S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-((N-(2-morpholinoethyl)methylsulfonamido)methyl)-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (0.125 g, 0.151 mmol, 36.4% yield, MS/ESI+ 827.03 [MH]+, [αD]=−28.63, c=0.8, DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.44 (s, 2H), 7.70-8.09 (m, 3H), 7.19 (d, 1H), 7.03-7.13 (m, 1H), 6.96 (dd, 1H), 7.08 (t, 1H), 6.02 (dd, 1H), 4.59 (s, 2H), 4.21-4.52 (m, 2H), 3.75-4.03 (m, 2H), 3.44-3.54 (m, 4H), 3.30-3.44 (m, 3H), 3.17-3.23 (m, 1H), 3.12 (s, 3H), 2.37 (t, 2H), 2.16-2.32 (m, 4H), 1.13-1.33 (m, 1H), 0.48-0.72 (m, 2H), 0.16-0.48 (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. customand the solvent removed under vacuum
  4. filtrationThe crude was purified by filtration through a silica cartridge (DCM:MeOH=98:2)
  5. customa further purification by flash chromatography on silica gel column (DCM:MeOH=99=1)

Sources & evidence

ORD record
ord-9491b82ece144750883632d919e782ce
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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