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Methanol → Methyl 6-(4-{1,2-dimethyl-1-[5-(pyridin-2-ylmethoxy)pyridin-2-yl]propyl}phenyl)pyridazine-3-carboxylate

HRID 1968670
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1968670
Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([CH3:32])([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=4)=[CH:20][N:19]=3)[CH:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.CN([CH:36]=[O:37])C.[CH3:38][OH:39]>C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:32][C:14]([C:11]1[CH:12]=[CH:13][C:8]([C:5]2[N:4]=[N:3][C:2]([C:38]([O:37][CH3:36])=[O:39])=[CH:7][CH:6]=2)=[CH:9][CH:10]=1)([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)=[CH:20][N:19]=1)[CH:15]([CH3:17])[CH3:16]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 3

HCID 887MethanolHCID 6228DimethylformamideHCID 57910808HCID 57910808, Verbindung

Produkt 1

HCID 57910811Methyl 6-(4-{1,2-dimethyl-1-[5-(pyridin-2-ylmethoxy)pyridin-2-yl]propyl}phenyl)pyridazine-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysator
HCID 635956
Ferrocene-1,1'-bis-(diphenylphosphine)
Katalysator
HCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

Palladium (II) acetate (8.00 mg, 0.0350 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (39.0 mg, 0.070 mmol) were added successively to a stirred solution of 5b (155 mg, 0349 mmol) in triethylamine:DMF:MeOH (4.00 mL of a 1:10:10 mixture, respectively) at rt. A gentle stream of the carbon monoxide gas was bubbled through the reaction mixture for approximately 15 min, after which the resulting mixture was heated to 70° C. under a carbon monoxide atmosphere (balloon) for about 5 h. After cooling to rt, the reaction mixture was filtered through a short column of CELITE®, eluting with DCM. The filtrate was partially concentrated in vacuo and diluted with EtOAc. The organic phase was washed with water, brine, dried (sodium sulfate) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 30%-100% EtOAc/hexanes as eluent) afforded the title compound 5c. m/z (ES) 469 (MH)+. 1HNMR (500 MHz, CDCl3): δ 8.62 (d, 1H, J=4.8 Hz), 8.41 (m, 1H), 8.22 (d, 1H, J=8.7 Hz), 8.08 (d, 2H, J=8.8 Hz), 7.96 (d, 1H, J=8.9 Hz), 7.75 (dt, 1H, J=1.7, 7.7 Hz), 7.56 (d, 2H, J=8.7 Hz), 7.53 (d, 1H, J=7.8 Hz), 7.26 (dd, 1H, J=5.2, 7.3 Hz), 7.19 (m, 2H), 5.23 (s, 2H), 4.10 (s, 3H), 3.11 (m, 1H, 6.6 Hz), 1.73 (s, 3H), 0.89 (d, 3H, J=6.7 Hz), 0.83 (d, 3H, J=6.8 Hz).

Aufarbeitung

  1. customat rt
  2. customA gentle stream of the carbon monoxide gas was bubbled through the reaction mixture for approximately 15 min
  3. temperatureAfter cooling to rt
  4. filtrationthe reaction mixture was filtered through a short column of CELITE®
  5. washeluting with DCM
  6. concentrationThe filtrate was partially concentrated in vacuo
  7. additiondiluted with EtOAc
  8. washThe organic phase was washed with water, brine
  9. dry with materialdried (sodium sulfate)
  10. concentrationconcentrated in vacuo
  11. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 30%-100% EtOAc/hexanes as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-3aa3c05255eb4e07854510897e2bf4f2
Quelldatensatz
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08426413B2

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