1,2-Dichloroethane → HCID 86681735, compound

HRID 571322Notes

Reaction equation

HRID 571322 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][N:9]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH:16]=[CH:17][N:18]3[CH2:23][C:24]([OH:26])=[O:25])[S:10]([CH3:13])(=[O:12])=[O:11])[CH2:3][CH2:2]1.[Cl:27][C:28]1[CH:29]=[N+:30]([O-:53])[CH:31]=[C:32]([Cl:52])[C:33]=1[CH2:34][C@@H:35]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH:44]([F:46])[F:45])=[C:39]([O:47][CH2:48][CH:49]2[CH2:51][CH2:50]2)[CH:38]=1)O.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:27][C:28]1[CH:29]=[N+:30]([O-:53])[CH:31]=[C:32]([Cl:52])[C:33]=1[CH2:34][C@@H:35]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH:44]([F:46])[F:45])=[C:39]([O:47][CH2:48][CH:49]2[CH2:51][CH2:50]2)[CH:38]=1)[O:25][C:24](=[O:26])[CH2:23][N:18]1[C:19]2[C:15](=[C:14]([N:9]([CH2:8][CH2:7][N:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[S:10]([CH3:13])(=[O:12])=[O:11])[CH:22]=[CH:21][CH:20]=2)[CH:16]=[CH:17]1

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 86681734HCID 86681734, compound

Product 1

HCID 86681735HCID 86681735, compoundYield 10.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-(N-(2-morpholinoethyl)methylsulfonamido)-1H-indol-1-yl)acetic acid (100 mg, 0.262 mmol) in DCM (5 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (110 mg, 0.262 mmol), EDC (151 mg, 0.786 mmol) and DMAP (64.1 mg, 0.524 mmol) were added, and the mixture was reacted overnight at room temperature. The solvent was evaporated and the residue was partitioned between 1N HCl (10 ml) and EtOAc; the aqueous phase was extracted with EtOAc, the combined organic layers were dried over sodium sulfate and the solvent was removed under vacuum. Three flash chromatographic column on silica gel (DCM/MeOH 97/3) were required to afford (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(4-(N-(2-morpholinoethyl)methylsulfonamido)-1H-indol-1-yl)acetoxy)ethyl)pyridine 1-oxide (21.4 mg, 0.027 mmol, 10.4% yield, MS/ESI+ 783.19 [MH]+, [αD]=+14.1, c=0.2 DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.50 (s, 2H), 7.34 (d, 1H), 7.07-7.21 (m, 5H), 6.90 (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), 3.80 (t, 2H), 3.46-3.54 (m, 4H), 3.41 (dd, 1H), 3.21 (dd, 1H), 3.09 (s, 3H), 2.32 (dd, 2H), 2.23-2.31 (m, 4H), 1.07-1.36 (m, 1H), 0.54-0.65 (m, 2H), 0.29-0.47 (m, 2H).

Workup

  1. customthe mixture was reacted overnight at room temperature
  2. customThe solvent was evaporated
  3. customthe residue was partitioned between 1N HCl (10 ml) and EtOAc
  4. extractionthe aqueous phase was extracted with EtOAc
  5. dry with materialthe combined organic layers were dried over sodium sulfate
  6. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-645b17a3bb6e46f6a746209d9eda589a
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

Loading…