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Hydrochloric Acid → 1-{2-[6-(3,3-Difluoropyrrolidin-1-yl)pyrimidin-4-yl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl}-1H-imidazole-4-carbonitrile

HRID 2039498
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2039498
Cl[C:2]1[CH:7]=[C:6]([NH:8][NH2:9])[N:5]=[CH:4][N:3]=1.Cl.[F:11][C:12]1([F:17])[CH2:16][CH2:15][NH:14][CH2:13]1.C(N(C(C)C)C(C)C)C.FC(F)(F)C(O)=O.CN([CH:37]=[C:38]([N:44]1[CH:48]=[C:47]([C:49]#[N:50])[N:46]=[CH:45]1)[C:39](OCC)=[O:40])C.Cl>O>[F:11][C:12]1([F:17])[CH2:16][CH2:15][N:14]([C:2]2[N:3]=[CH:4][N:5]=[C:6]([N:8]3[C:39](=[O:40])[C:38]([N:44]4[CH:48]=[C:47]([C:49]#[N:50])[N:46]=[CH:45]4)=[CH:37][NH:9]3)[CH:7]=2)[CH2:13]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 6

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 81531Diisopropylethylamine2×HCID 2472224-Chloro-6-hydrazinylpyrimidineHCID 249034823,3-Difluoropyrrolidine hydrochloride2×HCID 66726020Ethyl 3-(N,N-dimethylamino)-2-(4-cyano-1H-imidazol-1-yl)acrylate

Produkt

1
HCID 444651261-{2-[6-(3,3-Difluoropyrrolidin-1-yl)pyrimidin-4-yl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl}-1H-imidazole-4-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 200 mg (1.4 mmol) of the compound from Example 11A, 238 mg (1.7 mmol) of 3,3-difluoropyrrolidine hydrochloride and 289 μl (215 mg, 1.7 mmol) of N-ethyl-N-(propan-2-yl)propane-2-amine in 3 ml of water is stirred at 100° C. for 16 h. Following the addition of 53 μl (79 mg, 0.7 mmol) of trifluoroacetic acid and 324 mg (1.4 mmol) of the compound from Example 6A, the reaction mixture is stirred at 100° C. for 16 h. 1 ml of 1 N hydrochloric acid is added to the reaction mixture. The resulting precipitated hydrochloride of the crude product is filtered off, washed with diethyl ether and dried. The crude product still contains unreacted starting material (compound from Example 11A). Accordingly, the crude product is reacted with 108 μl (80 mg, 0.6 mmol) of N-ethyl-N-(propan-2-yl)propane-2-amine, 10 mg (0.1 mmol) of 3,3-difluoropyrrolidine hydrochloride and 2 ml of water in a single mode microwave (Emrys Optimizer) at 170° C. for 15 min The reaction solution purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient). Yield: 30 mg (6% of theory)

Aufarbeitung

  1. stirringthe reaction mixture is stirred at 100° C. for 16 h
  2. customThe resulting precipitated hydrochloride of the crude product
  3. filtrationis filtered off
  4. washwashed with diethyl ether
  5. customdried
  6. custompurified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient)

Quellen und Nachweise

ORD-Eintrag
ord-d19f2ba2716e409c9137f98ef07a0c9c
Quelldatensatz
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08580778B2

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