Tetrahydrofuran → 2-(3-{1-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorophenyl)propan-2-ol

HRID 515236Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 515236
[F:1][C:2]1([F:30])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([C:15]3[C:16]([F:26])=[C:17]([CH:23]=[CH:24][CH:25]=3)C(OCC)=O)=[CH:12][CH:13]=2)[N:8]([CH3:27])[S:7]1(=[O:29])=[O:28].[CH3:31][Mg]Br.[CH2:34]1[CH2:38][O:37]CC1>>[F:1][C:2]1([F:30])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([C:15]3[C:16]([F:26])=[C:17]([C:38]([OH:37])([CH3:34])[CH3:31])[CH:23]=[CH:24][CH:25]=3)=[CH:12][CH:13]=2)[N:8]([CH3:27])[S:7]1(=[O:29])=[O:28]

Komponenten

4

Edukt 3

HCID 8028TetrahydrofuranHCID 68245322Ethyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorobenzoateHCID 178418573HCID 178418573, Verbindung

Produkt 1

HCID 674099752-(3-{1-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorophenyl)propan-2-ol

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

Ethyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorobenzoate (37-1) (240 mg, 0.54 mmol, 1.0 eq) was dissolved in THF (4 mL). The reaction mixture was cooled to −78° C. and methylmagnesium bromide (0.91 mL, 2.7 mmol, 3.0 M, 5.0 eq) was added. The resulting mixture stirred at ambient temperature for 30 minutes. The reaction was quenched by the addition of NH4Cl (2 mL), extracted with EtOAc (50 mL), washed with water (10 mL) and brine (10 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (40 g SiO2, 10-70% EtOAc in hexanes) to afford 2-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorophenyl)propan-2-ol (37-2) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 7.81 (td, J=1.6, 7.6 Hz, 1 H); 7.59 (td, J=1.6, 7.6 Hz, 1 H); 7.42 (dd, J=2.0, 8.0 Hz, 1 H); 7.23 (t, J=7.6 Hz, 1 H); 7.06 (d, J=8.0 Hz, 1 H); 3.81-4.03 (m, 2 H); 3.49 (s, 3 H); 2.15 (m, 1 H); 1.69 (s, 6 H); 1.66 (m, 1 H); 1.39 (m, 1 H). HRMS m/z (M+H) 428.1242 found, 428.1250 required.

Aufarbeitung

  1. customThe reaction was quenched by the addition of NH4Cl (2 mL)
  2. extractionextracted with EtOAc (50 mL)
  3. washwashed with water (10 mL) and brine (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography (40 g SiO2, 10-70% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-5698607f0c5749c999bb14d43f0c6837
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108937B2

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