Hydrochloric Acid → N-{2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-5-methoxy-6-(pyridin-4-ylamino)pyrimidin-4-yl}-2-methoxyacetamide

HRID 1482931Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1482931
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]3[CH2:23][CH2:22][CH2:21][C:10]=3[N:11]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])[N:12]=2)[N:5]=[C:4]([NH:24][C:25](=[O:29])[CH2:26][O:27][CH3:28])[C:3]=1[O:30][CH3:31].Cl.Br[C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C=O)C.O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][N:11]1[C:10]2[CH2:21][CH2:22][CH2:23][C:9]=2[C:8]([C:6]2[N:5]=[C:4]([NH:24][C:25](=[O:29])[CH2:26][O:27][CH3:28])[C:3]([O:30][CH3:31])=[C:2]([NH:1][C:34]3[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=3)[N:7]=2)=[N:12]1

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 881004-Bromopyridinium chlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90015879N-{6-amino-2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxypyrimidin-4-yl}-2-methoxyacetamide

Produkt 1

HCID 72202406N-{2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-5-methoxy-6-(pyridin-4-ylamino)pyrimidin-4-yl}-2-methoxyacetamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

50 mg of N-{6-amino-2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxypyrimidin-4-yl}-2-methoxyacetamide 1-7-1 (0.12 mmol, 1.00 eq.), 25 mg of 4-bromopyridine hydrochloride (1:1) (0.13 mmol, 1.10 eq.), mg of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.02 mmol, 0.15 eq.), 115 mg of caesium carbonate (0.36 mmol, 3.00 eq.) and 2.6 mg of palladium diacetate (0.012 mmol, 0.1 eq.) were suspended in 0.5 mL of dry DMF and stirred under nitrogen atmosphere at 105° C. bath temperature for two h. The reaction mixture was diluted with water, the pH was adjusted to 7.5 using 4N aqueous hydrochloric acid and the crude product was extracted with DCM. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography yielding 29 mg (0.06 mmol, 49%) of analytically pure target compound.

Aufarbeitung

  1. extractionthe crude product was extracted with DCM
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography
  5. customyielding 29 mg (0.06 mmol, 49%) of analytically pure target compound

Quellen und Nachweise

ORD-Eintrag
ord-21409567c7e1445694d895a847b23b7a
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09416125B2

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