Sodium Carbonate → 4-(2,5-Difluorobenzyl)-6-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridine

HRID 2074690Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2074690
C([O-])([O-])=O.[Na+].[Na+].Br[C:8]1[CH:9]=[C:10]2[C:15](=[N:16][CH:17]=1)[NH:14][CH2:13][CH2:12][CH:11]2[CH2:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[F:26].[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][N:35]=2)[CH2:30][CH2:29]1>C1(C)C=CC=CC=1.C(O)C.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>[F:26][C:20]1[CH:21]=[CH:22][C:23]([F:25])=[CH:24][C:19]=1[CH2:18][CH:11]1[C:10]2[C:15](=[N:16][CH:17]=[C:8]([C:37]3[CH:36]=[N:35][C:34]([N:31]4[CH2:30][CH2:29][N:28]([CH3:27])[CH2:33][CH2:32]4)=[CH:39][CH:38]=3)[CH:9]=2)[NH:14][CH2:13][CH2:12]1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 27696181-Methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazineHCID 578858006-Bromo-4-(2,5-difluorobenzyl)-1,2,3,4-tetrahydro-[1,8]naphthyridine

Produkt 1

HCID 469067154-(2,5-Difluorobenzyl)-6-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1,2,3,4-tetrahydro-[1,8]naphthyridineAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 21863594Toluene ethanolLösungsmittel

Versuchsvorschrift

Na2CO3 (2N, 53 μL) (4.0 eq) was added to a mixture of 6-bromo-4-(2,5-difluorobenzyl)-1,2,3,4-tetrahydro-[1,8]naphthyridine (9.0 mg) (1 eq), 1-methyl-4-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl]piperazine (11.3 mg) (1.4 eq), and Pd(PPh3)4 (3.0 mg, 0.1 eq) in toluene/ethanol (4:1, v/v, 2 mL). The reaction was heated at 90° C. for six (6) hours. The reaction mixture was then concentrated under reduced pressure and the residue was taken up in CH2Cl2 (15 mL) and washed with water (15 mL). The organic phase was dried over Na2SO4, filtered, concentrated under reduced pressure, and purified by silica gel chromatography using a gradient of 0-20% methanol/CH2Cl2 as the eluting solvent to give the title compound as a yellow foam (26% yield). LCMS: m/z=436 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 1.7-2.0 (m, 2H), 2.37 (s, 3H), 2.55-2.60 (m, 4H), 2.81 (dd, J=9.1 and 13.3 Hz, 1H), 2.98 (dd, J=6.4 and 13.3H, 1H), 3.08-3.18 (m, 1H), 3.40-3.50 (m, 1H), 3.53-3.70 (m, 5H), 5.18 (bs, 1H), 6.68 (d, J=8.8 Hz, 1H), 6.81-6.87 (m, 1H), 6.89-6.96 (m, 1H), 6.98-7.06 (m, 1H), 7.16 (d, J=1 Hz, 1H), 7.50 (dd, J=2.5 and 8.8 Hz, 1H), 8.05 (d, J=1 Hz, 1H), 8.24 (d, J=2.5 Hz, 1H).

Aufarbeitung

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. washwashed with water (15 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. custompurified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-a07b89f0cba14bf79138532ca9d2a7c7
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919502B2

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