1,2-Dichloroethane → 4-((S)-2-((S)-3-(3-(2-(tert-Butoxycarbonylamino)ethylcarbamoyl)phenylsulfonyl)-thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-ethyl)-3,5-dichloropyridine 1-oxide

HRID 520340Notes

Reaction equation

HRID 520340 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([S:10]([N:13]2[CH2:17][CH2:16][S:15][C@H:14]2[C:18]([O:20][C@H:21]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH:39]([F:41])[F:40])=[C:34]([O:42][CH2:43][CH:44]3[CH2:46][CH2:45]3)[CH:33]=2)[CH2:22][C:23]2[C:28]([Cl:29])=[CH:27][N+:26]([O-:30])=[CH:25][C:24]=2[Cl:31])=[O:19])(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)([OH:3])=O.[NH2:47][CH2:48][CH2:49][NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54].C(Cl)CCl>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[C:53]([O:52][C:51]([NH:50][CH2:49][CH2:48][NH:47][C:1]([C:4]1[CH:5]=[C:6]([S:10]([N:13]2[CH2:17][CH2:16][S:15][C@H:14]2[C:18]([O:20][C@H:21]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH:39]([F:40])[F:41])=[C:34]([O:42][CH2:43][CH:44]3[CH2:46][CH2:45]3)[CH:33]=2)[CH2:22][C:23]2[C:24]([Cl:31])=[CH:25][N+:26]([O-:30])=[CH:27][C:28]=2[Cl:29])=[O:19])(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)=[O:3])=[O:57])([CH3:56])([CH3:55])[CH3:54]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 187201N-BOC-ethylenediamineHCID 710924964-((S)-2-((S)-3-(3-carboxyphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

Product 1

HCID 1185584624-((S)-2-((S)-3-(3-(2-(tert-Butoxycarbonylamino)ethylcarbamoyl)phenylsulfonyl)-thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-ethyl)-3,5-dichloropyridine 1-oxideYield 88.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-((S)-2-((S)-3-(3-Carboxyphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (200 mg, 0.278 mmol), tert-butyl 2-aminoethylcarbamate (89 mg, 0.556 mmol), DMAP (40.7 mg, 0.334 mmol) and EDC (160 mg, 0.834 mmol) were dissolved in DMF. The reaction was stirred at room temperature overnight to achieve completion. The reaction mixture was diluted with water, and the precipitate was washed with water, dissolved in ethyl acetate and extracted with HCl 1N, NaHCO3 5% and brine. The organic phase was dried over Na2SO4 and concentrated under vacuum to give 4-((S)-2-((S)-3-(3-(2-(tert-butoxycarbonylamino)ethylcarbamoyl)phenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (211 mg, 0.245 mmol, 88% yield).

Workup

  1. washthe precipitate was washed with water
  2. dissolutiondissolved in ethyl acetate
  3. extractionextracted with HCl 1N, NaHCO3 5% and brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-0af03a1bab444088a2be031d1d14abaa
Source dataset
uspto-grants-2016_05
Patent number
US09326976B2

Reaction notes

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