Dimethylformamide → 3-(1-cyano-1-methylethyl)-N-{3-[(2-{[(4,4-difluoropiperidin-1-yl)acetyl]amino}[1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino]-4-methylphenyl}benzamide

HRID 1800738Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1800738
Cl[CH2:2][C:3]([NH:5][C:6]1[S:7][C:8]2[N:9]=[C:10]([NH:15][C:16]3[CH:17]=[C:18]([NH:23][C:24](=[O:36])[C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:33])[CH3:32])[CH:26]=4)[CH:19]=[CH:20][C:21]=3[CH3:22])[N:11]=[CH:12][C:13]=2[N:14]=1)=[O:4].CN(C)C=O.C(N(CC)CC)C.Cl.[F:50][C:51]1([F:57])[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1>O1CCCC1.O>[C:34]([C:31]([C:27]1[CH:26]=[C:25]([CH:30]=[CH:29][CH:28]=1)[C:24]([NH:23][C:18]1[CH:19]=[CH:20][C:21]([CH3:22])=[C:16]([NH:15][C:10]2[N:11]=[CH:12][C:13]3[N:14]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][N:54]4[CH2:55][CH2:56][C:51]([F:57])([F:50])[CH2:52][CH2:53]4)[S:7][C:8]=3[N:9]=2)[CH:17]=1)=[O:36])([CH3:33])[CH3:32])#[N:35]

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 86646091N-[3-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino)-4-methylphenyl]-3-(1-cyano-1-methylethyl)benzamide

Produkt 1

HCID 595069793-(1-cyano-1-methylethyl)-N-{3-[(2-{[(4,4-difluoropiperidin-1-yl)acetyl]amino}[1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino]-4-methylphenyl}benzamideAusbeute 47,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of N-[3-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl}amino)-4-methylphenyl]-3-(1-cyano-1-methylethyl)benzamide (150 mg, 288 μmol) produced in Example D32(i) in tetrahydrofuran (4 mL)/N,N-dimethylformamide (0.5 mL) were added triethylamine (180 μL, 1.30 mmol) and 4,4-difluoropiperidine hydrochloride (68 mg, 432 μmol), and the mixture was stirred at 60° C. for 7 hr. To the reaction mixture was added water (15 mL), and the mixture was extracted with ethyl acetate (20 mL, 5 mL). The combined organic layer was washed with saturated brine (5 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=20/80→0/100), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate to give the title compound (82 mg, 47%) as colorless crystals.

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate (20 mL, 5 mL)
  2. washThe combined organic layer was washed with saturated brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=20/80→0/100)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-b6eff13cd8794bb7995f1223607435ee
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08344135B2

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