1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(4-(methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide

HRID 571281Notes

Reaction equation

HRID 571281 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8](=[O:20])[N:9]([CH2:16][C:17]([OH:19])=[O:18])[C:10]2=[O:15])(=[O:4])=[O:3].[Cl:21][C:22]1[CH:23]=[N+:24]([O-:47])[CH:25]=[C:26]([Cl:46])[C:27]=1[CH2:28][C@@H:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]([F:40])[F:39])=[C:33]([O:41][CH2:42][CH:43]2[CH2:45][CH2:44]2)[CH:32]=1)O.C(Cl)CCl>CN(C1C=CN=CC=1)C.C1COCC1.O>[Cl:21][C:22]1[CH:23]=[N+:24]([O-:47])[CH:25]=[C:26]([Cl:46])[C:27]=1[CH2:28][C@@H:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]([F:40])[F:39])=[C:33]([O:41][CH2:42][CH:43]2[CH2:45][CH2:44]2)[CH:32]=1)[O:18][C:17](=[O:19])[CH2:16][N:9]1[C:8](=[O:20])[C:7]2[C:11](=[CH:12][CH:13]=[CH:14][C:6]=2[NH:5][S:2]([CH3:1])(=[O:3])=[O:4])[C:10]1=[O:15]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 866816892-(4-(Methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetic acid

Product 1

HCID 86681690(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(4-(methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxideYield 21.29%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(4-(methylsulfonamido)-1,3-dioxoisoindolin-2-yl)acetic acid (78 mg, 0.262 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-hydroxyethyl)pyridine 1-oxide (110 mg, 0.262 mmol), DMAP (15.97 mg, 0.131 mmol) and EDC (125 mg, 0.654 mmol) in 15 ml of THF was stirred at room temperature for 2 days. The mixture was diluted with water, acidified and extracted twice with EtOAc; the organic layer was then washed with brine, dried over sodium sulfate and evaporated. The residue was triturated with methanol and the title compound was obtained as a pale yellow solid (39 mg, 0.056 mmol, 21.29% yield, MS/ESI+ 700.11 [MH]+, [αD]=−63.94, c=0.355 in DCM). 1H NMR (300 MHz, DMSO-d6) δ ppm 9.29 (br. s., 1H), 8.47 (s, 2H), 7.86 (dd, 1H), 7.81 (dd, 1H), 7.63 (dd, 1H), 7.19 (d, 1H), 7.10 (d, 1H), 6.97 (dd, 1H), 7.08 (t, 1H), 6.02 (dd, 1H), 4.46 (d, 1H), 4.38 (d, 1H), 3.93 (d, 2H), 3.41 (dd, 1H), 3.30 (s, 3H), 3.24 (dd, 1H), 1.10-1.31 (m, 1H), 0.48-0.66 (m, 2H), 0.27-0.48 (m, 2H)

Workup

  1. extractionextracted twice with EtOAc
  2. washthe organic layer was then washed with brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customThe residue was triturated with methanol

Sources & evidence

ORD record
ord-f1c420855fc74c42a799f273e6ef12f2
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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