1,2-Dichloroethane → HCID 86681746, compound

HRID 571330Notes

Reaction equation

HRID 571330 reaction equation
Cl.[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([CH2:24][C:25]([OH:27])=[O:26])[C:19](=[O:28])[CH2:18]3)[S:11]([CH3:14])(=[O:13])=[O:12])[CH2:4][CH2:3]1.[Cl:29][C:30]1[CH:31]=[N+:32]([O-:55])[CH:33]=[C:34]([Cl:54])[C:35]=1[CH2:36][C@@H:37]([C:39]1[CH:44]=[CH:43][C:42]([O:45][CH:46]([F:48])[F:47])=[C:41]([O:49][CH2:50][CH:51]2[CH2:53][CH2:52]2)[CH:40]=1)O.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:29][C:30]1[CH:31]=[N+:32]([O-:55])[CH:33]=[C:34]([Cl:54])[C:35]=1[CH2:36][C@@H:37]([C:39]1[CH:44]=[CH:43][C:42]([O:45][CH:46]([F:48])[F:47])=[C:41]([O:49][CH2:50][CH:51]2[CH2:53][CH2:52]2)[CH:40]=1)[O:26][C:25](=[O:27])[CH2:24][N:20]1[C:21]2[C:17](=[CH:16][C:15]([N:10]([CH2:9][CH2:8][N:5]3[CH2:6][CH2:7][O:2][CH2:3][CH2:4]3)[S:11]([CH3:14])(=[O:13])=[O:12])=[CH:23][CH:22]=2)[CH2:18][C:19]1=[O:28]

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 86681744HCID 86681744, compound

Product 1

HCID 86681746HCID 86681746, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-(5-(N-(2-morpholinoethyl)methylsulfonamido)-2-oxoindolin-1-yl)acetic acid hydrochloride (0.105 g, 0.242 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (0.092 g, 0.220 mmol), EDC (0.127 g, 0.660 mmol), and DMAP (0.054 g, 0.440 mmol) in DCM (15 ml) was stirred at room temperature for 24 hours. The mixture was diluted with DCM and washed with aqueous sat. NH4Cl and aqueous 5% NaHCO3; the organic phase was dried over sodium sulfate and the solvent was removed. The crude was purified by flash chromatography on silica gel column (DCM:MeOH=99:1 to 96:4) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N-(2-morpholinoethyl)-methylsulfonamido)-2-oxoindolin-1-yl)acetoxy)ethyl)pyridine 1-oxide (0.070 g, 0.088 mmol, 39.8% yield, MS/ESI+ 799.46 [MH]+, [αD]=−40.88, c=0.25, MeOH). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.44 (s, 2H), 7.32 (s, 1H), 7.26 (dd, 1H), 7.19 (d, 1H), 7.11 (d, 1H), 6.97 (dd, 1H), 6.83 (d, 1H), 7.07 (t, 1H), 6.03 (dd, 1H), 4.61 (d, 1H), 4.50 (d, 1H), 3.95 (d, 2H), 3.70 (t, 2H), 3.67 (s, 2H), 3.48-3.57 (m, 4H), 3.39 (dd, 1H), 3.22 (dd, 1H), 3.07 (s, 3H), 2.30-2.43 (m, 6H), 1.14-1.34 (m, 1H), 0.50-0.69 (m, 2H), 0.25-0.46 (m, 2H).

Workup

  1. washwashed with aqueous sat. NH4Cl and aqueous 5% NaHCO3
  2. dry with materialthe organic phase was dried over sodium sulfate
  3. customthe solvent was removed
  4. customThe crude was purified by flash chromatography on silica gel column (DCM:MeOH=99:1 to 96:4)

Sources & evidence

ORD record
ord-0cfaf0952bf5430da6d745504b9d49c4
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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