1,2-Dichloroethane → HCID 86681712, compound

HRID 571304Notes

Reaction equation

HRID 571304 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.[CH3:33][N:34]([CH3:57])[CH2:35][CH2:36][N:37]([C:42]1[CH:43]=[C:44]2[C:48](=[CH:49][CH:50]=1)[C:47](=[O:51])[N:46]([CH2:52][C:53](O)=[O:54])[C:45]2=[O:56])[S:38]([CH3:41])(=[O:40])=[O:39]>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:53](=[O:54])[CH2:52][N:46]1[C:45](=[O:56])[C:44]2[C:48](=[CH:49][CH:50]=[C:42]([N:37]([CH2:36][CH2:35][N:34]([CH3:33])[CH3:57])[S:38]([CH3:41])(=[O:39])=[O:40])[CH:43]=2)[C:47]1=[O:51]

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 86681710HCID 86681710, compound

Product 1

HCID 86681712HCID 86681712, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (180 mg, 0.428 mmol), DMAP (52.3 mg, 0.428 mmol) and EDC (164 mg, 0.857 mmol) in DCM (10 ml), 2-(5-(N-(2-(dimethylamino)ethyl)methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetic acid hydrochloride (191 mg, 0.471 mmol) was added portion wise within 4 hours, and the reaction was stirred at room temperature for 24 hours. The solvent was evaporated and the crude was purified by flash silica gel chromatography (DCM/MeOH 10/0.2) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(5-(N-(2-(dimethylamino)ethyl)methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide as a white solid (253 mg, 0.328 mmol, 77% yield). MS/ESI+ 771.15 [MH]+, [αD]=−32.18, c=0.353, DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.43 (s, 2H), 7.93-8.00 (m, 2H), 7.89 (dd, 1H), 7.19 (d, 1H), 7.09 (d, 1H), 6.97 (dd, 1H), 7.08 (t, 1H), 6.02 (dd, 1H), 4.43 (s, 2H), 3.92-4.05 (m, 2H), 3.88 (t, 2H), 3.39 (dd, 1H), 3.23 (dd, 1H), 3.13 (s, 3H), 2.31 (t, 2H), 2.10 (s, 6H), 1.07-1.33 (m, 1H), 0.49-0.71 (m, 2H), 0.27-0.49 (m, 2H)

Workup

  1. customThe solvent was evaporated
  2. customthe crude was purified by flash silica gel chromatography (DCM/MeOH 10/0.2)

Sources & evidence

ORD record
ord-bd80d8f19b6d4a8abf9e55bbf9680826
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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