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Hydrochloric Acid → 9-Cyclopentyl-N-(5-(4-((dimethylamino)acetyl)-1-piperazinyl)-2-pyridinyl)-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 79186
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 79186
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH2:15])[N:13]=[CH:14][C:9]=3[C:8]3[CH:16]=[CH:17][N:18]=[C:19]([F:20])[C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:22]1[N:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][N:31]([C:34](=[O:39])[CH2:35][N:36]([CH3:38])[CH3:37])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].Cl>C([O-])([O-])=O.[K+].[K+].CO.C(O)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].C(OCC)C.O1CCOCC1>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:22]4[CH:23]=[CH:24][C:25]([N:28]5[CH2:33][CH2:32][N:31]([C:34](=[O:39])[CH2:35][N:36]([CH3:37])[CH3:38])[CH2:30][CH2:29]5)=[CH:26][N:27]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:16]=[CH:17][N:18]=[C:19]([F:20])[C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

12

Edukt 5

HCID 313Hydrochloric AcidHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 582996521-(4-(6-Chloropyridin-3-yl)piperazin-1-yl)-2-(dimethylamino)ethanoneHCID 582996889-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Produkt 1

HCID 58299625
9-Cyclopentyl-N-(5-(4-((dimethylamino)acetyl)-1-piperazinyl)-2-pyridinyl)-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine
Ausbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 6

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 702EthanolLösungsmittelHCID 887MethanolLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 11430Potassium CarbonateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A 10 mL reaction vessel was charged with compound 245 (100 mg, 369 μmol), compound 300 (109 mg, 387 μmol), tris(dibenzylideneacetone)dipalladium (0) (25.3 mg, 27.6 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (32.0 mg, 55.3 μmol), sodium t-butoxide (70.8 mg, 737 μmol), and dioxane (2.5 mL). The reaction was purged with argon and heated with microwave energy (300 W) for 2.5 hours at 120° C. The reaction was added to aqueous K2CO3 (10%, 30 mL) and extracted with dichloromethane+10% methanol (3×30 mL). The combined organics were dried (MgSO4) and evaporated to give an orange oil. Preparative reverse phase HPLC (gradient elution 0.1% TFA in water/10-70% acetonitrile) afforded. a yellow oil. This residue was taken up in aqueous K2CO3 (30 mL) and extracted with dichloromethane+10% methanol (3×30 mL). The combined organics were dried (MgSO4) and evaporated to give a yellow solid. This was taken up in methanol (2 mL) and 1M HCl in ethanol (0.5 mL) was added. Diethyl ether (10 mL) was added to precipitate the product, which was filtered and dried in vacuo to give compound 299 as a yellow solid (32 mg, 17%). 1H NMR (500 MHz, DMSO-d6) δ 9.43-9.61 (m, 1 H) 9.27-9.40 (m, 1 H) 8.01-8.12 (m, 1 H) 7.91-8.01 (m, 1 H) 7.75-7.91 (m, 3 H) 7.62-7.75 (m, 1 H) 5.27-5.42 (m, 1 H) 4.14-4.28 (m, 3 H) 3.10-3.18 (m, 3 H) 3.06 (none, 3 H) 2.68 (d, J=4.65 Hz, 8 H) 2.06-2.18 (m, 2 H) 1.93-2.06 (m, 2 H) 1.80-1.93 (m, 3 H) 1.48-1.69 (m, 3 H) ppm.

Aufarbeitung

  1. customA 10 mL reaction vessel
  2. customThe reaction was purged with argon
  3. additionThe reaction was added to aqueous K2CO3 (10%, 30 mL)
  4. extractionextracted with dichloromethane+10% methanol (3×30 mL)
  5. dry with materialThe combined organics were dried (MgSO4)
  6. customevaporated
  7. customto give an orange oil
  8. washPreparative reverse phase HPLC (gradient elution 0.1% TFA in water/10-70% acetonitrile)
  9. customafforded
  10. extractionextracted with dichloromethane+10% methanol (3×30 mL)
  11. dry with materialThe combined organics were dried (MgSO4)
  12. customevaporated
  13. customto give a yellow solid
  14. customto precipitate the product, which
  15. filtrationwas filtered
  16. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-b62670fff73d41a682f036cccabccba1
Quelldatensatz
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08841312B2

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