1,2-Dichloroethane → HCID 86681729, compound

HRID 571319Notes

Reaction equation

HRID 571319 reaction equation
FC(F)(F)C(O)=O.[O:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[N:26]([CH2:30][C:31]([OH:33])=[O:32])[CH:25]=[CH:24]3)[S:17]([CH3:20])(=[O:19])=[O:18])[CH2:10][CH2:9]1.[Cl:34][C:35]1[CH:36]=[N+:37]([O-:60])[CH:38]=[C:39]([Cl:59])[C:40]=1[CH2:41][C@@H:42]([C:44]1[CH:49]=[CH:48][C:47]([O:50][CH:51]([F:53])[F:52])=[C:46]([O:54][CH2:55][CH:56]2[CH2:58][CH2:57]2)[CH:45]=1)O.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[ClH:34].[Cl:34][C:35]1[CH:36]=[N+:37]([O-:60])[CH:38]=[C:39]([Cl:59])[C:40]=1[CH2:41][C@@H:42]([C:44]1[CH:49]=[CH:48][C:47]([O:50][CH:51]([F:53])[F:52])=[C:46]([O:54][CH2:55][CH:56]2[CH2:58][CH2:57]2)[CH:45]=1)[O:32][C:31](=[O:33])[CH2:30][N:26]1[C:27]2[C:23](=[CH:22][C:21]([N:16]([CH2:15][CH2:14][N:11]3[CH2:12][CH2:13][O:8][CH2:9][CH2:10]3)[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:29][CH:28]=2)[CH:24]=[CH:25]1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687HCID 71092687, compoundHCID 86681731HCID 86681731, compound

Product 1

HCID 86681729HCID 86681729, compoundYield 47.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of crude 2-(5-(N-(2-morpholinoethyl)methylsulfonamido)-1H-indol-1-yl)acetic acid 2,2,2-trifluoroacetate (150 mg, 0.303 mmol) in DCM, (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (165 mg, 0.393 mmol), EDC (226 mg, 1.180 mmol) and DMAP (24.02 mg, 0.197 mmol) were added, and the resulting mixture was stirred overnight at room temperature. The solvent was removed, and the residue was purified by flash chromatography on silica gel (DCM/MeOH 95/5). The obtained compound was treated with 4N HCl in dioxane (30 ml) affording after evaporation of the volatiles (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(2-(5-(N-(2-morpholinoethyl)methylsulfonamido)-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide hydrochloride (76.3 mg, 0.093 mmol, 32% yield, MS/ESI+ 783.47 [MH]+, [αD]=−17.52, c=0.25 in DCM). 1H NMR (300 MHz, DMSO-d6+Na2CO3) δ ppm 8.50 (s, 2H), 7.34 (d, 1H), 7.07-7.23 (m, 5H), 6.89 (dd, 1H), 7.06 (t, 1H), 6.55 (d, 1H), 6.02 (dd, 1H), 5.25 (d, 1H), 5.10 (d, 1H), 3.91 (d, 2H), 3.77-3.85 (m, 2H), 3.46-3.52 (m, 4H), 3.39-3.47 (m, 1H), 3.16-3.25 (m, 1H), 3.09 (s, 3H), 2.30-2.36 (m, 2H), 2.24-2.31 (m, 4H), 1.10-1.24 (m, 1H), 0.52-0.67 (m, 2H), 0.23-0.47 (m, 2H).

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by flash chromatography on silica gel (DCM/MeOH 95/5)
  3. additionThe obtained compound was treated with 4N HCl in dioxane (30 ml)
  4. customaffording

Sources & evidence

ORD record
ord-726400c347c8462594d3e4f0cfb255f7
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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