1,2-Dichloroethane → HCID 89512127, compound

HRID 571217Notes

Reaction equation

HRID 571217 reaction equation
[C:1]([O:5][C:6]([N:8]([C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[CH:16][N:17]2[CH2:22][C:23]([OH:25])=[O:24])[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>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]([C:13]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[CH:16][N:17]2[CH2:22][C:23]([O:25][C@H:34]([C:36]1[CH:41]=[CH:40][C:39]([O:42][CH:43]([F:44])[F:45])=[C:38]([O:46][CH2:47][CH:48]2[CH2:49][CH2:50]2)[CH:37]=1)[CH2:33][C:32]1[C:31]([Cl:51])=[CH:30][N+:29]([O-:52])=[CH:28][C:27]=1[Cl:26])=[O:24])[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 89518061HCID 89518061, compound

Product 1

HCID 89512127HCID 89512127, compoundYield 80.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-1H-indol-1-yl)acetic acid (250 mg, 0.679 mmol) in DCM (10 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (285 mg, 0.679 mmol), EDC (390 mg, 2.036 mmol) and DMAP (41.5 mg, 0.339 mmol) were added, and the mixture was reacted at room temperature overnight. The mixture was partitioned between DCM and 1N HCl and the aqueous phase was extracted with DCM (3×20 ml); the solvent was removed to give (S)-4-(2-(2-(4-(N-(tert-butoxycarbonyl)-methylsulfonamido)-1H-indol-1-yl)acetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (420 mg, 0.545 mmol, 80% yield). MS/ESI+ 770.9 [MH]+. This intermediate was used in the following steps without purification.

Workup

  1. customthe mixture was reacted at room temperature overnight
  2. customThe mixture was partitioned between DCM and 1N HCl
  3. extractionthe aqueous phase was extracted with DCM (3×20 ml)
  4. customthe solvent was removed

Sources & evidence

ORD record
ord-218d0082f96f4f629700cef7026cf217
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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