Potassium Phosphate, Tribasic → 3-(4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methylpyrimidin-5-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole

HRID 872059Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 872059
Br[C:2]1[C:3]([O:9][CH2:10][C@H:11]2[CH2:13][C@@H:12]2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][N:15]=2)=[N:4][C:5]([CH3:8])=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:30]2[CH:34]=[N:33][N:32]3[CH2:35][CH2:36][CH2:37][C:31]=23)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1COCC1.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([C@H:12]2[CH2:13][C@@H:11]2[CH2:10][O:9][C:3]2[C:2]([C:30]3[CH:34]=[N:33][N:32]4[CH2:35][CH2:36][CH2:37][C:31]=34)=[CH:7][N:6]=[C:5]([CH3:8])[N:4]=2)=[N:15][CH:16]=1

Komponenten

9

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 710613855-bromo-4-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidineHCID 710628193-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4H,5H,6H-pyrrolo[1,2-b]pyrazole

Produkt 1

HCID 714886763-(4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methylpyrimidin-5-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 5-bromo-4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]-methoxy}-2-methylpyrimidine (2-3) (120 mg, 0.3 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (OO2) (104 mg, 0.4 mmol), tripotassium phosphate (145 mg, 0.7 mmol), S-Phos (14 mg, 0.03 mmol), and Pd(OAc)2 (3.9 mg, 0.02 mmol) in THF (1.5 mL) and water (0.3 mL) was heated at 100° C. for 14 hours. The reaction mixture was allowed to cool to room temperature. The mixture was then diluted with EtOAc (10 mL), washed with sodium bicarbonate (2 mL) and brine (2 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier) to afford the title compound as a colorless gum. 1H NMR (500 MHz, DMSO): δ 8.51 (s, 1 H), 8.14 (d, J=2.9 Hz, 1 H), 7.84 (s, 1 H), 7.31-7.22 (m, 2 H), 4.53 (dd, J=11.3, 6.4 Hz, 1 H), 4.25 (dd, J=11.3, 8.2 Hz, 1 H), 4.04 (t, J=7.3 Hz, 2 H), 3.78 (s, 3 H), 2.97 (t, J=7.3 Hz, 2 H), 2.50 (s, 3 H), 2.39-2.32 (m, 2 H), 2.19 (dd, J=8.4, 4.7 Hz, 1 H), 1.79 (m, 1 H), 1.17 (dt, J=8.6, 4.5 Hz, 1 H), 1.06 (dd, J=8.6, 4.9 Hz, 1 H); HRMS m/z (M+H) 378.1921 found, 378.1925 required.

Aufarbeitung

  1. temperatureto cool to room temperature
  2. washwashed with sodium bicarbonate (2 mL) and brine (2 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier)

Quellen und Nachweise

ORD-Eintrag
ord-3cc8ecd0997f4e5182910b276a20fb00
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08975261B2

Notizen zur Reaktion

Wird geladen…