1,2-Dichloroethane → HCID 89511671, compound

HRID 571223Notes

Reaction equation

HRID 571223 reaction equation
[C:1]([O:5][C:6]([N:8]([C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]([CH2:22][C:23]([OH:25])=[O:24])[CH:14]=1)[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:26][C:27]1[CH:28]=[N+:29]([O-:52])[CH:30]=[C:31]([Cl:51])[C:32]=1[CH2:33][C@@H:34]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:45])[F:44])=[C:38]([O:46][CH2:47][CH:48]2[CH2:50][CH2:49]2)[CH:37]=1)O.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]([C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]([CH2:22][C:23]([O:25][C@H:34]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:44])[F:45])=[C:38]([O:46][CH2:47][CH:48]3[CH2:49][CH2:50]3)[CH:37]=2)[CH2:33][C:32]2[C:31]([Cl:51])=[CH:30][N+:29]([O-:52])=[CH:28][C:27]=2[Cl:26])=[O:24])[CH:14]=1)[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687HCID 71092687, compoundHCID 89518063HCID 89518063, compound

Product 1

HCID 89511671HCID 89511671, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-(3-(N-(tert-butoxycarbonyl)methylsulfonamido)-1H-indol-1-yl)acetic acid (220 mg, 0.597 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (228 mg, 0.543 mmol), EDC (312 mg, 1.629 mmol) and DMAP (66.3 mg, 0.543 mmol) in dry DCM (10 ml), under nitrogen, was stirred at room temperature for 24 hours. The mixture was washed with aqueous 5% citric acid, with water and then with brine; the organic phase was dried over Na2SO4 and evaporated to dryness. The crude was purified by flash chromatography on silica gel (DCM:ethyl acetate=6:4) to give (S)-4-(2-(2-(3-(N-(tert-butoxycarbonyl)-methylsulfonamido)-1H-indol-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (297 mg, 0.385 mmol, 71% yield). MS/ESI+ 770.0 [MH]+.

Workup

  1. washThe mixture was washed with aqueous 5% citric acid, with water
  2. dry with materialthe organic phase was dried over Na2SO4
  3. customevaporated to dryness
  4. customThe crude was purified by flash chromatography on silica gel (DCM:ethyl acetate=6:4)

Sources & evidence

ORD record
ord-ce166cc696d8443f914b478a3960439a
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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