1,2-Dichloroethane → HCID 86681705, compound

HRID 571298Notes

Reaction equation

HRID 571298 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[OH:10].C(Cl)CCl.Cl.[O:33]=[C:34]1[C:42]2[C:37](=[CH:38][C:39]([N:43]([CH2:48][CH2:49][N:50]3[CH2:55][CH2:54][CH2:53][CH2:52][CH2:51]3)[S:44]([CH3:47])(=[O:46])=[O:45])=[CH:40][CH:41]=2)[C:36](=[O:56])[N:35]1[CH2:57][C:58](O)=[O:59]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[O:10][C:58](=[O:59])[CH2:57][N:35]1[C:36](=[O:56])[C:37]2[C:42](=[CH:41][CH:40]=[C:39]([N:43]([CH2:48][CH2:49][N:50]3[CH2:51][CH2:52][CH2:53][CH2:54][CH2:55]3)[S:44]([CH3:47])(=[O:46])=[O:45])[CH:38]=2)[C:34]1=[O:33]

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 86681703HCID 86681703, compound

Product 1

HCID 86681705HCID 86681705, compoundYield 52.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (188 mg, 0.449 mmol), DMAP (110 mg, 0.897 mmol) and EDC (129 mg, 0.673 mmol) in DCM (10 ml), 2-(1,3-dioxo-5-(N-(2-(piperidin-1-yl)ethyl)methylsulfonamido)isoindolin-2-yl)acetic acid hydrochloride (200 mg, 0.449 mmol) was added portion wise over 5 hours, and the resulting mixture was stirred at room and for 96 hours. The solvent was removed and the crude was purified by silica gel chromatography (EtOAc/DCM 2/1 then DCM/MeOH 100/3). The resulting white solid was triturated with EtOH and recovered by filtration affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(1,3-dioxo-5-(N-(2-(piperidin-1-yl)ethyl)methylsulfonamido)isoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (190 mg, 0.234 mmol, 52.2% yield, LC-MS purity (BPI): 98.3%, MS/ESI+ 811.21 [MH]+, [αD]=+28.12, c=0.653 DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.44 (s, 2H), 7.97 (d, 1H), 7.95 (d, 1H), 7.89 (dd, 1H), 7.19 (d, 1H), 7.09 (d, 1H), 6.96 (dd, 1H), 7.08 (t, 1H), 6.02 (dd, 1H), 4.43 (s, 2H), 3.91-4.04 (m, 2H), 3.88 (t, 2H), 3.38 (dd, 1H), 3.23 (dd, 1H), 3.15 (s, 3H), 2.35 (t, 2H), 2.17-2.31 (m, 4H), 1.03-1.53 (m, 7H), 0.49-0.68 (m, 2H), 0.28-0.46 (m, 2H).

Workup

  1. customThe solvent was removed
  2. customthe crude was purified by silica gel chromatography (EtOAc/DCM 2/1
  3. customThe resulting white solid was triturated with EtOH
  4. filtrationrecovered by filtration

Sources & evidence

ORD record
ord-8ba8726f89224365972ff3e286a9ad30
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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