Phenylboronic Acid → (7R,8R,9R)-10-acetyl-3,9-diphenyl-7-(2-methoxyethoxy)-2-methyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

HRID 723408Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 723408
[C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:18])=[C:16](Br)[N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([O:19][CH2:20][CH2:21][O:22][CH3:23])[C@H:6]([O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[C@H:5]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=[O:3])[CH3:2].[C:37]1(B(O)O)[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.[F-].[K+].P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>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].C1COCC1>[C:1]([N:4]1[C:13]2[C:12]3=[N:14][C:15]([CH3:18])=[C:16]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[N:11]3[CH:10]=[CH:9][C:8]=2[C@@H:7]([O:19][CH2:20][CH2:21][O:22][CH3:23])[C@H:6]([O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[C@H:5]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=[O:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 66827Phenylboronic AcidHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 69586421HCID 69586421, Verbindung

Produkt 1

HCID 69586312(7R,8R,9R)-10-acetyl-3,9-diphenyl-7-(2-methoxyethoxy)-2-methyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

2.61 g (4.67 mmol) (7R,8R,9R)-10-acetyl-3-bromo-7-(2-methoxyethoxy)-2-methyl-9-phenyl-8-pivaloyloxy-7.8.9.10-tetrahydroimidazo[1.2-h][1.7]naphthyridine, 0.63 g (5.14 mmol) phenylboronic acid, 0.89 g (15.4 mmol) KF (spray-dried), 0.14 g (0.15 mmol) Pd2(dba)3, 0.07g (0.36 mmol/10wt % solution in hexane)P(t-Bu)3 and THF (30 ml) are added to a Schlenk tube under argon. Afterwards the Schlenk tube is evacuated and refilled with argon in a freeze-pump-thaw cycles technique three times. The reaction mixture is stirred under argon for 2 d at 25° C. Subsequently the reaction is diluted by adding of ethyl acetate and then filtrated through silica gel. The concentrated crude product is purified by column chromatography (diethyl ether/petrol ether: 6/4) to give 1.80 g (3.24 mmol/70%) of the title compound as an amorphous colourless solid. 1H-NMR (200 MHz, [D6] DMSO): δ=1.20 (s, 9H), 2.20(s, 3H), 2.43(s, 3H), 3.30 (s, 3H), 3.40–3.57(m, 2H), 3.88 (t, 2H), 4.64 (d, 1H), 5.35 (t, 1H), 5.83(d, 1H), 7.00(d, 1H), 7.10–7.30(m, 5H), 7.41–7.68 (m, 5H), 8.24(d, 1H).

Aufarbeitung

  1. customAfterwards the Schlenk tube is evacuated
  2. additionrefilled with argon in a freeze-pump-thaw cycles technique three times
  3. additionSubsequently the reaction is diluted
  4. additionby adding of ethyl acetate
  5. filtrationfiltrated through silica gel
  6. concentrationThe concentrated crude product
  7. customis purified by column chromatography (diethyl ether/petrol ether: 6/4)

Quellen und Nachweise

ORD-Eintrag
ord-c428b6b6c48347bc98f348eb0deb5cc7
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07141567B2

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