1,2-Dichloroethane → HCID 86681708, compound

HRID 571301Notes

Reaction equation

HRID 571301 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].C(Cl)CCl.[O:32]=[C:33]1[C:41]2[C:36](=[CH:37][C:38]([N:42]([CH2:47][C:48]3[S:49][CH:50]=[CH:51][CH:52]=3)[S:43]([CH3:46])(=[O:45])=[O:44])=[CH:39][CH:40]=2)[C:35](=[O:53])[N:34]1[CH2:54][C:55](O)=[O:56]>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:55](=[O:56])[CH2:54][N:34]1[C:35](=[O:53])[C:36]2[C:41](=[CH:40][CH:39]=[C:38]([N:42]([CH2:47][C:48]3[S:49][CH:50]=[CH:51][CH:52]=3)[S:43]([CH3:46])(=[O:45])=[O:44])[CH:37]=2)[C:33]1=[O:32]

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 86681707HCID 86681707, compound

Product 1

HCID 86681708HCID 86681708, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (200 mg, 0.476 mmol), DMAP (116 mg, 0.952 mmol), and EDC (182 mg, 0.952 mmol) in DCM (10 ml), 2-(1,3-dioxo-5-(N-(thiophen-2-ylmethyl)methylsulfonamido)isoindolin-2-yl)acetic acid (225 mg, 0.571 mmol) was added portion wise, and the resulting mixture was stirred at room temperature for 18 hours. The solvent was evaporated, and the crude was purified by flash chromatography on silica gel (DCM/MeOH 10/0.5). The resulting product was triturated with iPr2O affording after filtration 227 mg of crude desired product. A further purification by flash chromatography on silica gel (DCM/acetone 8/1) was performed to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(1,3-dioxo-5-(N-(thiophen-2-ylmethyl)methylsulfonamido)isoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (155 mg, 0.195 mmol, 40.9% yield, MS/ESI+ 796.02 [MH]+, [αD]=−30.31, c=0.415, DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.38 (s, 2H), 7.96 (d, 1H), 7.91 (d, 1H), 7.86 (dd, 1H), 7.40 (dd, 1H), 7.19 (d, 1H), 7.08 (d, 1H), 6.92-6.99 (m, 1H), 7.08 (t, 1H), 6.86 (d, 1H), 6.84 (d, 1H), 6.00 (dd, 1H), 5.25 (s, 2H), 4.39 (s, 2H), 3.81-4.09 (m, 2H), 3.37 (dd, 1H), 3.21 (s, 3H), 3.21 (dd, 1H), 1.17-1.37 (m, 1H), 0.50-0.69 (m, 2H), 0.21-0.46 (m, 2H)

Workup

  1. customThe solvent was evaporated
  2. customthe crude was purified by flash chromatography on silica gel (DCM/MeOH 10/0.5)
  3. customThe resulting product was triturated with iPr2O affording
  4. filtrationafter filtration 227 mg of crude desired product
  5. customA further purification by flash chromatography on silica gel (DCM/acetone 8/1)

Sources & evidence

ORD record
ord-b254568a4f5945cca706ba4afdec7971
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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