1,2-Dichloroethane → HCID 86681601, compound

HRID 571178Notes

Reaction equation

HRID 571178 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:28]([O:32][C:33]([NH:35][C:36]1[CH:44]=[C:43]2[C:39]([CH2:40][N:41]([CH2:46][C:47](O)=[O:48])[C:42]2=[O:45])=[CH:38][CH:37]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29].C(Cl)CCl>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[C:28]([O:32][C:33]([NH:35][C:36]1[CH:44]=[C:43]2[C:39]([CH2:40][N:41]([CH2:46][C:47]([O:10][C@H:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]4[CH2:25][CH2:24]4)[CH:12]=3)[CH2:8][C:7]3[C:6]([Cl:26])=[CH:5][N+:4]([O-:27])=[CH:3][C:2]=3[Cl:1])=[O:48])[C:42]2=[O:45])=[CH:38][CH:37]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide2×HCID 86681600HCID 86681600, compound

Product 1

HCID 86681601HCID 86681601, compoundYield 69.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (Compound 7, 60 mg, 0.143 mmol), 2-(6-(tert-butoxycarbonylamino)-1-oxoisoindolin-2-yl)acetic acid (65.6 mg, 0.214 mmol), DMAP (20.93 mg, 0.171 mmol), and EDC (82 mg, 0.428 mmol) were dissolved in DMF (5 ml). The reaction was stirred at RT overnight. The reaction mixture was diluted with water, and the precipitate was washed with water, dissolved in EtOAc and extracted with HCl 1N, Na2CO3 sat. sol. and brine. The organic phase was dried over Na2SO4 and concentrated under vacuum to give (S)-4-(2-(2-(6-(tert-butoxycarbonylamino)-1-oxoisoindolin-2-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (70 mg, 0.099 mmol, 69% yield). MS/ESI+ 306.12 [MH]+

Workup

  1. washthe precipitate was washed with water
  2. dissolutiondissolved in EtOAc
  3. extractionextracted with HCl 1N, Na2CO3 sat. sol. and brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-ff1fdee909ff4c5b9c9f10a4465d3e15
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

Loading…