Water → HCID 71553994, compound

HRID 571344Notes

Reaction equation

HRID 571344 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:37])[CH:5]=[C:6]([Cl:36])[C:7]=1[CH2:8][C@@H:9]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH:32]([F:34])[F:33])=[C:27]([OH:35])[CH:26]=1)[O:10][C:11](=[O:24])[CH2:12][N:13]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]1=[O:23].C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH:55]2[CH2:59][CH2:58][O:57][CH2:56]2)(=O)=O)=CC=1.O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:37])[CH:5]=[C:6]([Cl:36])[C:7]=1[CH2:8][C@@H:9]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH:32]([F:34])[F:33])=[C:27]([O:35][CH:55]2[CH2:59][CH2:58][O:57][CH2:56]2)[CH:26]=1)[O:10][C:11](=[O:24])[CH2:12][N:13]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]1=[O:23]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 13837325Tetrahydrofuran-3-yl 4-methylbenzenesulfonateHCID 86681761HCID 86681761, compound

Product 1

HCID 71553994HCID 71553994, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-3,5-dichloro-4-(2-(4-(difluoromethoxy)-3-hydroxyphenyl)-2-(2-(1,3-dioxoisoindolin-2-yl)acetoxy)ethyl)pyridine 1-oxide (155 mg, 0.280 mmol) in DMF (3.8 ml), potassium carbonate (46.5 mg, 0.336 mmol) was added, and the mixture stirred at RT for 30 minutes. Tetrahydrofuran-3-yl 4-methylbenzenesulfonate (224 mg, 0.924 mmol) was added, and the mixture stirred at RT overnight. Water was added, and the aqueous phase extracted with AcOEt (2×). The organic phase was washed with brine, dried and evaporated under reduced pressure. The crude was purified through preparative HPLC (Method 2) to give 17 mg of title compound (yield 10%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.45 (s, 2H), 7.92 (d, J=4.41 Hz, 4H), 7.18-7.27 (m, 1H), 7.05 (m, 2H), 6.98 (d, J=7.94 Hz, 1H), 6.02 (dd, J=8.38, 4.85 Hz, 1H), 5.12 (m, 1H), 4.30-4.58 (m, 2H), 3.62-4.06 (m, 4H), 3.14-3.43 (m, 2H), 2.20 (ddd, J=13.56, 6.73, 6.62 Hz, 1H), 1.86-2.05 (m, 1H). MS/ESI+ [M+H]+=622.7

Workup

  1. stirringthe mixture stirred at RT overnight
  2. extractionthe aqueous phase extracted with AcOEt (2×)
  3. washThe organic phase was washed with brine
  4. customdried
  5. customevaporated under reduced pressure
  6. customThe crude was purified through preparative HPLC (Method 2)

Sources & evidence

ORD record
ord-2d2dfad597394542bea42c9dd2a5e8de
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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