Methanol → HCID 68425418, Verbindung

HRID 1802496Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1802496
[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][C:11]1[C:20]2[CH:21]=[CH:22][N:23]=[C:24]([O:25][CH2:26][CH3:27])[C:19]=2[C:18]2[C:13](=[CH:14][CH:15]=[N:16][CH:17]=2)[N:12]=1.[Cl:28][C:29]1[CH:34]=[C:33](I)[CH:32]=[C:31]([Cl:36])[C:30]=1[NH:37][C:38]1[C:47]2[CH:48]=[CH:49][N:50]=[C:51]([O:52][CH3:53])[C:46]=2[C:45]2[C:40](=[CH:41][CH:42]=[N:43][CH:44]=2)[N:39]=1.CN(C1C=CC=CN=1)C.C(N(C(C)C)CC)(C)C.[CH3:72][OH:73]>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][C:11]1[C:20]2[CH:21]=[CH:22][N:23]=[C:24]([O:25][CH2:26][CH3:27])[C:19]=2[C:18]2[C:13](=[CH:14][CH:15]=[N:16][CH:17]=2)[N:12]=1)[C:51]([O:52][CH3:53])=[O:73].[Cl:28][C:29]1[CH:34]=[C:33]([CH:32]=[C:31]([Cl:36])[C:30]=1[NH:37][C:38]1[C:47]2[CH:48]=[CH:49][N:50]=[C:51]([O:52][CH3:53])[C:46]=2[C:45]2[C:40](=[CH:41][CH:42]=[N:43][CH:44]=2)[N:39]=1)[C:72]([O:25][CH3:24])=[O:73]

Komponenten

9

Edukt 5

HCID 887MethanolHCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 59436020HCID 59436020, VerbindungHCID 59436035HCID 59436035, Verbindung

Produkt 2

HCID 68425418HCID 68425418, VerbindungHCID 68668103HCID 68668103, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 98885Molybdenum carbonyl (Mo(CO)6)KatalysatorHCID 167845palladium(II) acetateKatalysator

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

The carbonylation reaction was conducted following the procedure described in J. Comb. 2003, 5, 350. To a solution of N-(2,6-dichloro-4-iodophenyl)-10-ethoxypyrido[4,3-c]-1,6-naphthyridin-6-amine (Example 152, Step 1) (130 mg, 0.39 mmol) and N-(2,6-dichloro-4-iodophenyl)-10-methoxypyrido[4,3-c]-1,6-naphthyridin-6-amine (Example 152, Step 1) (66 mg, 0.13 mol) in methanol (5 mL) were added dimethylamino pyridine (96 mg, 0.78 mmol), diisopropylethylamine (137 uL, 0.78 mmol), molybdenumhexacarbonyl (106 mg, 0.39 mmol) and palladium (II) acetate (9 mg, 0.39 mmol). The solution was heated in a microwave reactor at 150° C. for 15 min. The black solution was extracted with EtOAc and water, dried with MgSO4, filtered, and concentrated under reduced pressure. Purification by chromatography on silica gel (100% hexanes to 100% EtOAc) afforded methyl 3,5-dichloro-4-[(10-ethoxypyrido[4,3-c]-1,6-naphthyridin-6-yl)amino]benzoate and methyl 3,5-dichloro-4-[(10-methoxypyrido[4,3-c]-1,6-naphthyridin-6-yl)amino]benzoate. The mixture of esters (117 mg, 0.27 mmol) were suspended in CHCl3 (5 mL) followed by addition of BBr3 (1.91 mL, 1.91 mmol). The reaction mixture was heated to 85° C. for 45 min. After cooling to room temperature, the solution was extracted with EtOAc and saturated NaHCO3, dried with MgSO4, filtered, and concentrated. Purification by chromatography on silica gel (100% CH2Cl2 to 70% CH2Cl2/30% MeOH) afforded the title compound.

Aufarbeitung

  1. customThe carbonylation reaction
  2. extractionThe black solution was extracted with EtOAc and water
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by chromatography on silica gel (100% hexanes to 100% EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-e43411c6437147b482ddcde2eb8ca0d4
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08349865B2

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