Potassium Carbonate → 4-[1-cyano-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-benzoic acid tert-butyl ester

HRID 1773914

Reaktionsgleichung

Reaktionsgleichung von HRID 1773914
I[C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:3]=1[C:24]#[N:25].[C:26]([O:30][C:31](=[O:47])[C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:33]=1)([CH3:29])([CH3:28])[CH3:27].C([O-])([O-])=O.[K+].[K+]>C1COCC1.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]>[C:26]([O:30][C:31](=[O:47])[C:32]1[CH:37]=[CH:36][C:35]([C:2]2[N:11]=[C:10]3[N:4]([CH2:5][CH2:6][C:7]4[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=4[CH:9]3[O:12][CH:13]3[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH2:18]3)[C:3]=2[C:24]#[N:25])=[CH:34][CH:33]=1)([CH3:29])([CH3:27])[CH3:28]

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 43767661,1-Dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 867039962-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carbonitrile

Produkt 1

HCID 867039954-[1-cyano-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-benzoic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a solution of 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carbonitrile (example 221) (215 mg, 0.48 mmole) in THF (3 mL) are added 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid tert-butyl ester (191 mg, 0.63 mmole), 1M aqueous K2CO3 (2 mL) and PdCl2(dppf)2 (20 mg). The flask is evacuated and filled with argon. The reaction mixture is heated at 85° C. for 24 hours. AcOEt is added and the organic phase is washed with water, dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH) (100:0) to (95:5) to give 4-[1-cyano-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-benzoic acid tert-butyl ester melting at 95° C.

Aufarbeitung

  1. customThe flask is evacuated
  2. additionfilled with argon
  3. additionAcOEt is added
  4. washthe organic phase is washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customThe residue is purified by silica gel chromatography
  9. washeluting with (CH2Cl2:MeOH) (100:0) to (95:5)

Quellen und Nachweise

ORD-Eintrag
ord-6cd14e08c47b48af9bfa6f9c25617101
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09255101B2

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