1,2-Dichloroethane → HCID 89455815, compound

HRID 1776602Notes

Reaction equation

HRID 1776602 reaction equation
[C:1]([O:5][C:6]([N:8]([C:13]1[CH:14]=[C:15]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])[C:16]([S:18][CH2:19][C:20]([OH:22])=[O:21])=[O:17])[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.[Cl:32][C:33]1[CH:34]=[N+:35]([O-:58])[CH:36]=[C:37]([Cl:57])[C:38]=1[CH2:39][C@@H:40]([C:42]1[CH:47]=[CH:46][C:45]([O:48][CH:49]([F:51])[F:50])=[C:44]([O:52][CH2:53][CH:54]2[CH2:56][CH2:55]2)[CH:43]=1)O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]([C:13]1[CH:14]=[C:15]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])[C:16]([S:18][CH2:19][C:20]([O:22][C@H:40]([C:42]1[CH:47]=[CH:46][C:45]([O:48][CH:49]([F:50])[F:51])=[C:44]([O:52][CH2:53][CH:54]2[CH2:55][CH2:56]2)[CH:43]=1)[CH2:39][C:38]1[C:37]([Cl:57])=[CH:36][N+:35]([O-:58])=[CH:34][C:33]=1[Cl:32])=[O:21])=[O:17])[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 111,2-Dichloroethane2×HCID 71092687HCID 71092687, compoundHCID 89459982HCID 89459982, compound

Product 1

HCID 89455815HCID 89455815, compoundYield 24.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(3-(N-(tert-butoxycarbonyl)methylsulfonamido)-4-methoxybenzoylthio)acetic acid (0.206 g, 0.491 mmol) in dry DCM (16 ml), EDC (0.157 g, 0.818 mmol) and DMAP (0.050 g, 0.409 mmol) were added followed by (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.172 g, 0.409 mmol), and the resulting solution was stirred overnight at RT. Additional EDC (0.080 g, 0.42 mmol) and DMAP (0.025 g, 0.20 mmol) were added, and the reaction was stirred at the same temperature for 24 hours. The mixture was partitioned between DCM and HCl 1N; the organic phase was washed with aqueous NaHCO3 and dried over Na2SO4. The solvent was removed and the crude was purified by preparative HPLC affording (S)-4-(2-(2-(3-(N-(tert-butoxycarbonyl)methylsulfonamido)-4-methoxybenzoylthio)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (0.082 g, 0.100 mmol, 24.4% yield, MS/ESI+ 821.1 [MH]+).

Workup

  1. stirringthe reaction was stirred at the same temperature for 24 hours
  2. customThe mixture was partitioned between DCM and HCl 1N
  3. washthe organic phase was washed with aqueous NaHCO3
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed
  6. customthe crude was purified by preparative HPLC

Sources & evidence

ORD record
ord-7b6253040c544752af142fc58b9aed0f
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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