Potassium Phosphate, Tribasic → HCID 58631240, Verbindung

HRID 1824285

Reaktionsgleichung

Reaktionsgleichung von HRID 1824285
Br[C:2]1[N:3]=[CH:4][C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[O:8][CH3:9].C1(P(C2CCCCC2)C2C=CC=CC=2C2C3C(C4C=CC=CC=4C=2)=CC=CC=3)CCCCC1.[Cl:54][C:55]1[CH:60]=[C:59]([Cl:61])[CH:58]=[CH:57][C:56]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Cl:54][C:55]1[CH:60]=[C:59]([Cl:61])[CH:58]=[CH:57][C:56]=1[C:2]1[N:3]=[CH:4][C:5]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][C@@H:12]2[OH:20])=[N:6][C:7]=1[O:8][CH3:9]

Komponenten

8

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 2734659(2,4-Dichlorophenyl)boronic acid4×HCID 22147288Dicyclohexyl(2-(phenanthren-9-yl)phenyl)phosphaneHCID 58631232HCID 58631232, Verbindung

Produkt 1

HCID 58631240HCID 58631240, VerbindungAusbeute 31 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator4×HCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A Kimble vial was charged with (1R,2S)-1-[(5-bromo-6-methoxypyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol (0.55 g, 1.63 mmol), Pd2(dba)3 (33 mg, 35 μmol), dicyclohexyl[2-(9-phenanthryl)phenyl]phosphine (64 mg), 2,4-dichlorophenylboronic acid (567 mg, 2.67 mmol), K3PO4 (1.13 g, 5.34 mmol) and toluene (15 mL). The vial was flushed with N2, sealed and heated at 110° C. for 6 hr. Cool to rt, add additional Pd2(dba)3 (33 mg) and 2,4-dichlorophenylboronic acid (0.5 g, 2.7 mmol). Continue heating overnight. Add additional Pd2(dba)3 (33 mg) and 2,4-dichlorophenylboronic acid (0.5 g, 2.7 mmol) and continue heating for 5 hr. Add additional Pd2(dba)3 (33 mg) and 2,4-dichlorophenylboronic acid (0.5 g, 2.7 mmol) and continue heating overnight. The reaction was cooled to rt, diluted with CH2Cl2, washed with sat. aq NaHCO3 and sat. aq. NaCl. Dry organic extract over MgSO4, filter and concentrate. Purify by biotage MPLC (90 g column, 30% ethyl acetate/hexanes) to afford 0.2 g (31%) of (1R,2S)-1-{[5-(2,4-dichlorophenyl)-6-methoxypyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol as an oil: 1H NMR (CDCl3) δ 3.06–3.10, 3.26–3.32, 3.92, 4.79, 5.33, 5.49–5.50, 7.28–7.41, 7.50, 7.74; MS (ESI+) for C20H17Cl2N3O2 m/z 402 (M+H)+.

Aufarbeitung

  1. customThe vial was flushed with N2
  2. customsealed
  3. temperatureCool to rt
  4. temperatureContinue heating overnight
  5. temperaturecontinue heating for 5 hr
  6. temperaturecontinue heating overnight
  7. temperatureThe reaction was cooled to rt
  8. washwashed with sat. aq NaHCO3 and sat. aq. NaCl
  9. extractionDry organic extract over MgSO4
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurify by biotage MPLC (90 g column, 30% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-fa40eef091624b7f9555f45b80caf6d5
Quelldatensatz
uspto-grants-2006_05
Patentnummer
US07041672B2

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