Potassium Phosphate, Tribasic → HCID 86698333, Verbindung

HRID 1183066Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1183066
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[CH:17]=[O:18].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[C:51]1[CH:52]=[C:53]([NH:57][C:58](=[O:63])[CH2:59][CH:60]([CH3:62])[CH3:61])[CH:54]=[N:55][CH:56]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CN(C=O)C>[CH:17]([C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:51]3[CH:52]=[C:53]([NH:57][C:58](=[O:63])[CH2:59][CH:60]([CH3:61])[CH3:62])[CH:54]=[N:55][CH:56]=3)[CH:3]=2)[N:7]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[N:6]=1)=[O:18]

Komponenten

10

Edukt 5

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 205807365-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehydeHCID 68195779N-(5-Bromo-3-Pyridinyl)-3-Methylbutamide

Produkt 1

HCID 86698333HCID 86698333, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A solution of 5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde (II) (498 mg, 1.4 mmol), bis(pinacolato)diboron (426 mg, 1.6 mmol), KOAc (412 mg, 4.2 mmol) and dry DMF (10 mL) was purged with nitrogen. Pd(dppf)2Cl2 (68 mg, 0.08 mmol) was added to the reaction and purged again with nitrogen. The solution was heated at 90° C. for 2 h. Once TLC showed the disappearance of (II), the solution was cooled to room temperature. To this solution was added K3PO4 (446 mg, 2.1 mmol), N-(5-bromopyridin-3-yl)-3-methylbutanamide (XXVIII) (358 mg, 1.4 mmol), Pd(PPh3)4 (48 mg, 0.042 mmol) and water (2 mL). The solution was purged with nitrogen and heated at 90° C. for 4 h. The reaction was passed through a pad of Celite® and then concentrated under reduced pressure. The residue was suspended in water, sonicated, filtered and dried. The crude product was purified on a silica gel column (100% DCM 3:97 MeOH:DCM) to give N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-3-methylbutanamide (LXXXIV) as an off white solid (239 mg, 0.59 mmol, 42% yield). 1H NMR (DMSO-d6, 500 MHz) δ ppm 0.96 (d, 6H), 1.60-1.67 (m, 1H), 1.75-1.84 (m, 1H), 2.05-2.15 (m, 3H), 2.26 (d, 2H), 2.39-2.47 (m, 1H), 3.80-3.86 (m, 1H), 3.89-3.93 (m, 1H), 6.13 (dd, 1H), 7.91 (dd, 1H), 8.06 (d, 1H), 8.36 (s, 1H), 8.39 (s, 1H), 8.63 (d, 1H), 8.81 (d, 1H), 10.23 (s, 1H); ESIMS found C23H26N4O3 m/z 407.3 (M+H).

Aufarbeitung

  1. custompurged again with nitrogen
  2. temperaturethe solution was cooled to room temperature
  3. customThe solution was purged with nitrogen
  4. temperatureheated at 90° C. for 4 h
  5. concentrationconcentrated under reduced pressure
  6. customsonicated
  7. filtrationfiltered
  8. customdried
  9. customThe crude product was purified on a silica gel column (100% DCM 3:97 MeOH:DCM)

Quellen und Nachweise

ORD-Eintrag
ord-a0d0f20860b74280bba6a7c78fff148a
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08664241B2

Notizen zur Reaktion

Wird geladen…