Sodium Carbonate → (R)-6-(2-methoxypyrimidin-5-yl)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole

HRID 2040970Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2040970
Br[C:2]1[CH:21]=[CH:20][C:5]2[N:6]=[C:7]([N:9]3[CH2:13][CH2:12][C@@H:11]([N:14]4[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]4)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[CH3:22][O:23][C:24]1[N:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][N:25]=1.C1CCC(P(C2C(C3C=CC=CC=3)=CC=CC=2)C2CCCCC2)CC1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)C.O1CCOCC1>[CH3:22][O:23][C:24]1[N:29]=[CH:28][C:27]([C:2]2[CH:21]=[CH:20][C:5]3[N:6]=[C:7]([N:9]4[CH2:13][CH2:12][C@@H:11]([N:14]5[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]5)[CH2:10]4)[S:8][C:4]=3[CH:3]=2)=[CH:26][N:25]=1

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 44124247(R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazoleHCID 534405922-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

Produkt 1

HCID 44124248(R)-6-(2-methoxypyrimidin-5-yl)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 22560076Dioxan ethanolLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A stirred mixture of (R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole (Example 14, 37.0 mg, 0.10 mmol), 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (31 mg, 0.13 mmol), dichlorobis(triphenylphosphine)palladium (II) (7.0 mg, 0.01 mmol), (2-biphenyl)dicyclohexylphosphine (3.5 mg, 0.01 mmol) in 1:1 ethanol/dioxane (0.40 mL) was treated with 1 M aqueous sodium carbonate (0.150 mL, 0.15 mmol). The reaction tube was sealed and the stirred mixture was heated to 150° C. under microwave irradiation for 10 minutes. The reaction mixture was cooled to room temperature then diluted with dichloromethane (2 mL) and filtered through diatomaceous earth, followed by an acetonitrile/dichloromethane rinse (10 mL). The filtrate was dried (Na2SO4) and concentrated under reduced pressure and the residue was purified by silica gel chromatography (70:30:0 to 63:30:7 dichloromethane/acetonitrile/methanol). Fractions containing product were combined and concentrated under reduced pressure to give (R)-6-(2-methoxypyrimidin-5-yl)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole. 1H NMR (300 MHz, CD2Cl2) δ ppm 1.43-1.50 (m, 2H), 1.61 (pentet, J=5 Hz, 4H), 2.00 (pentet, J=10 Hz, 1H), 2.24-2.31 (m, 1H), 2.40-2.58 (m, 4H), 3.01 (pentet, J=8 Hz, 1H), 3.40 (t, J=9 Hz, 1H), 3.50-3.57 (m, 1H), 3.73 (t, J=9 Hz, 1H), 3.79-3.86 (m, 1H), 4.02 (s, 3H), 7.44 (dd, J=2, 8 Hz, 1H), 7.56 (d, J=8 Hz, 1H), 7.78 (d, J=2 Hz, 1H), 8.72 (s, 2H); MS (ESI) m/z 396 (M+H)+.

Aufarbeitung

  1. customThe reaction tube was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered through diatomaceous earth
  4. washrinse (10 mL)
  5. dry with materialThe filtrate was dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (70:30:0 to 63:30:7 dichloromethane/acetonitrile/methanol)
  8. additionFractions containing product
  9. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-2d1d4e658abb4d05b424b2330a060488
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08580968B2

Notizen zur Reaktion

Wird geladen…