Hydrochloric Acid → (1-(6-((9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)-amino)-3-pyridinyl)-4-piperidinyl)methanol

HRID 79176

Reaktionsgleichung

Reaktionsgleichung von HRID 79176
[Si]([O:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:17]=[CH:18][C:19]([NH:22][C:23]3[N:24]=[CH:25][C:26]4[C:31]5[CH:32]=[CH:33][N:34]=[C:35]([F:36])[C:30]=5[N:29]([CH:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)[C:27]=4[N:28]=3)=[N:20][CH:21]=2)[CH2:12][CH2:11]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])([O-])=O.[K+].[K+].Cl>C1COCC1.CO.C(O)C.C(OCC)C>[CH:37]1([N:29]2[C:27]3[N:28]=[C:23]([NH:22][C:19]4[N:20]=[CH:21][C:16]([N:13]5[CH2:12][CH2:11][CH:10]([CH2:9][OH:8])[CH2:15][CH2:14]5)=[CH:17][CH:18]=4)[N:24]=[CH:25][C:26]=3[C:31]3[CH:32]=[CH:33][N:34]=[C:35]([F:36])[C:30]2=3)[CH2:38][CH2:39][CH2:40][CH2:41]1

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 58300053N-(5-(4-(((tert-Butyl(dimethyl)silyl)oxy)methyl)-1-piperidinyl)-2-pyridinyl)-9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Produkt 1

HCID 58299866(1-(6-((9-cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)-amino)-3-pyridinyl)-4-piperidinyl)methanolAusbeute 27,5 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 702EthanolLösungsmittelHCID 887MethanolLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Compound 282 (118 mg, 205 μmol) was dissolved in dry THF (3 mL). Tetrabutylammonium fluoride, 1.0M in THF (0.75 mL, 750 μmol) was added and the reaction was stirred at room temperature for 80 minutes. The resulting solution was added to aqueous K2CO3 (10%, 30 mL) and extracted with dichloromethane+10% methanol (2×30 mL). The combined organics were dried (MgSO4) and evaporated to give an orange oil. Silica gel chromatography (gradient elution ethyl acetate+2.5% TEA/0-5% methanol) afforded a yellow solid. This residue was taken up in methanol (1.5 mL) and HCl in ethanol (1.0M, 0.5 mL) was added. Diethyl ether (20 mL) was added to precipitate the product as a yellow solid, which was filtered and dried in vacuo to give compound 283 as a yellow solid (26 mg, 27%). 1H NMR (500 MHz, DMSO-d6) δ 9.87 (s, 1 H) 9.27-9.37 (m, 1 H) 8.11 (d, J=9.05 Hz, 1 H) 7.99-8.06 (m, 4 H) 7.48 (dd, J=9.17, 2.81 Hz, 1 H) 5.46 (quin, J=9.11 Hz, 1 H) 4.50 (t, J=5.26 Hz, 2 H) 3.70 (d, J=11.98 Hz, 2 H) 2.61-2.71 (m, 2 H) 2.35 (d, J=12.72 Hz, 2 H) 2.10 (br. s., 2 H) 1.95-2.06 (m, 2 H) 1.77 (t, 4 H) 1.45-1.59 (m, 1 H) 1.28 (qd, J=12.23, 3.67 Hz, 2 H) ppm.

Aufarbeitung

  1. extractionextracted with dichloromethane+10% methanol (2×30 mL)
  2. dry with materialThe combined organics were dried (MgSO4)
  3. customevaporated
  4. customto give an orange oil
  5. washSilica gel chromatography (gradient elution ethyl acetate+2.5% TEA/0-5% methanol)
  6. customafforded a yellow solid
  7. customto precipitate the product as a yellow solid, which
  8. filtrationwas filtered
  9. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-33920f27e82c410eb951179f33872381
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841312B2

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