1,2-Dichloroethane → HCID 86681657, compound

HRID 571241Notes

Reaction equation

HRID 571241 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]([OH:15])=[O:14])[C:7](=[O:16])[CH2:6]2.[Cl:17][C:18]1[CH:19]=[N+:20]([O-:43])[CH:21]=[C:22]([Cl:42])[C:23]=1[CH2:24][C@@H:25]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH:34]([F:36])[F:35])=[C:29]([O:37][CH2:38][CH:39]2[CH2:41][CH2:40]2)[CH:28]=1)O.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:17][C:18]1[CH:19]=[N+:20]([O-:43])[CH:21]=[C:22]([Cl:42])[C:23]=1[CH2:24][C@@H:25]([C:27]1[CH:32]=[CH:31][C:30]([O:33][CH:34]([F:36])[F:35])=[C:29]([O:37][CH2:38][CH:39]2[CH2:41][CH2:40]2)[CH:28]=1)[O:14][C:13](=[O:15])[CH2:12][N:8]1[C:9]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)[CH2:6][C:7]1=[O:16]

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 83755600HCID 83755600, compound

Product 1

HCID 86681657HCID 86681657, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(5-methoxy-2-oxoindolin-1-yl)acetic acid (200 mg, 0.904 mmol) in DCM (30 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (380 mg, 0.904 mmol), EDC (520 mg, 2.71 mmol) and DMAP (55.2 mg, 0.452 mmol) were added, and the mixture was reacted at room temperature overnight. The solvent was evaporated, and the resulting crude was partitioned between DCM (20 ml) and a 1N HCl (20 ml), and the desired compound was extracted with ethyl acetate (3×20 ml). The combined organic layers were dried over sodium sulfate and the solvent was removed. The crude was purified by flash chromatography on silica gel (DCM:MeOH 98:2) recovering the title compound (149.2 mg, 0.239 mmol, 27% yield). MS/ESI+ 623.12 [MH]+; [αD]=+19.12 c=0.5 in DCM; 1H NMR (300 MHz, DMSO-d6) δ ppm 8.45 (s, 2H), 7.18 (d, 1H), 7.06 (d, 1H), 6.92-6.98 (m, 2H), 7.07 (t, 1H), 6.76 (dd, 1H), 6.64 (d, 1H), 6.02 (dd, 1H), 4.54 (d, 1H), 4.46 (d, 1H), 3.91 (d, 2H), 3.74 (s, 3H), 3.59 (s, 2H), 3.40 (dd, 1H), 3.21 (dd, 1H), 1.03-1.41 (m, 1H), 0.50-0.70 (m, 2H), 0.21-0.50 (m, 2H).

Workup

  1. customthe mixture was reacted at room temperature overnight
  2. customThe solvent was evaporated
  3. customthe resulting crude was partitioned between DCM (20 ml)
  4. extractiona 1N HCl (20 ml), and the desired compound was extracted with ethyl acetate (3×20 ml)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. customthe solvent was removed
  7. customThe crude was purified by flash chromatography on silica gel (DCM:MeOH 98:2)

Sources & evidence

ORD record
ord-0442f8ddee374d93b934afdaebcb8ecd
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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