Hydrochloric Acid → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)-benzyloxy)-3-oxopropanoyloxy)ethyl)pyridine 1-oxide

HRID 1776490Notes

Reaction equation

HRID 1776490 reaction equation
C(OC([N:8]([C:13]1[CH:52]=[CH:51][C:16]([CH2:17][O:18][C:19](=[O:50])[CH2:20][C:21]([O:23][C@H:24]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH:42]([F:44])[F:43])=[C:37]([O:45][CH2:46][CH:47]3[CH2:49][CH2:48]3)[CH:36]=2)[CH2:25][C:26]2[C:31]([Cl:32])=[CH:30][N+:29]([O-:33])=[CH:28][C:27]=2[Cl:34])=[O:22])=[CH:15][C:14]=1[O:53][CH2:54][CH:55]1[CH2:57][CH2:56]1)[S:9]([CH3:12])(=[O:11])=[O:10])=O)(C)(C)C.Cl>C(Cl)Cl.O1CCOCC1>[Cl:34][C:27]1[CH:28]=[N+:29]([O-:33])[CH:30]=[C:31]([Cl:32])[C:26]=1[CH2:25][C@@H:24]([C:35]1[CH:40]=[CH:39][C:38]([O:41][CH:42]([F:43])[F:44])=[C:37]([O:45][CH2:46][CH:47]2[CH2:48][CH2:49]2)[CH:36]=1)[O:23][C:21](=[O:22])[CH2:20][C:19]([O:18][CH2:17][C:16]1[CH:51]=[CH:52][C:13]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[C:14]([O:53][CH2:54][CH:55]2[CH2:57][CH2:56]2)[CH:15]=1)=[O:50]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86679439(S)-4-(2-(3-(4-(N-(tert-butoxycarbonyl)-methylsulfonamido)-3-(cyclopropylmethoxy)benzyloxy)-3-oxopropanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

Product 1

HCID 71542917(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)-benzyloxy)-3-oxopropanoyloxy)ethyl)pyridine 1-oxideYield 16.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

(S)-4-(2-(3-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzyloxy)-3-oxopropanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (70 mg, 0.08 mmol) was dissolved in DCM (1 ml), and HCl 4M in Dioxane (500 μM) was added. The mixture was stirred at RT for 3 hours. The reaction was quenched with water, and the product was extracted with EtOAc. The organic phase was dried over Na2SO4 and evaporated to dryness. The crude was purified by Preparative reverse-phase HPLC to yield 10 mg of the final product (Yield: 16%).

Workup

  1. customThe reaction was quenched with water
  2. extractionthe product was extracted with EtOAc
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customevaporated to dryness
  5. customThe crude was purified by Preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-e18bb6828c2b478a9fbf82b449777177
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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