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Ethyl Acetate → 4-[4-(6-Methanesulfonyl-2-methyl-pyridin-3-ylamino)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931616
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1931616
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22](Cl)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][S:25]([C:28]1[N:33]=[C:32]([CH3:34])[C:31]([NH2:35])=[CH:30][CH:29]=1)(=[O:27])=[O:26].CC(C)([O-])C.[Na+].C(OCC)(=O)C>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([NH:35][C:31]4[C:32]([CH3:34])=[N:33][C:28]([S:25]([CH3:24])(=[O:27])=[O:26])=[CH:29][CH:30]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 4

HCID 8857Ethyl AcetateHCID 23676156Sodium t-butoxideHCID 510505272-Methyl-6-(methylsulfonyl)pyridin-3-amine2×HCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2×

Produkt 1

HCID 579650384-[4-(6-Methanesulfonyl-2-methyl-pyridin-3-ylamino)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester
Ausbeute 46,5 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecaneKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

A mixture of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 50 mg, 0.15 mmol), 6-methanesulfonyl-2-methyl-pyridin-3-ylamine (Intermediate 4; 28 mg, 0.15 mmol), palladium acetate (0.33 mg, 0.01 equivalent), sodium tert-butoxide (34 mg, 0.36 mmol), and 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (Aldrich, 1 mg, 0.02 equivalents) in dimethylformamide (2 mL) was heated in the microwave oven at 160° C. for 10 min. Ethyl acetate and water were added, and the aqueous layer was extracted three times with ethyl acetate. The ethyl acetate layers were combined, evaporated, and purified by preparative C18 HPLC, eluting with 10-100% acetonitrile/water. Samples containing the product were extracted twice with dichloromethane and the solvent was evaporated under high vacuum to give 4-[4-(6-methanesulfonyl-2-methyl-pyridin-3-ylamino)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (34 mg, 46%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 1.41 (s, 9H), 1.92-2.00 (m, 4H), 2.55 (s, 3H), 2.90-3.04 (m, 2H), 3.30 (water peak and SO2CH3 peak), 4.00-4.12 (m, 2H), 4.84-4.96 (m, 1H), 7.92 (d, 1H, J=8.5 Hz), 8.22-8.36 (m, 3H), 10.06 (br s, 1H). HRMS Calcd. for C22H30N7O4S (MH+): 488.2075. Found: 488.2073.

Aufarbeitung

  1. extractionthe aqueous layer was extracted three times with ethyl acetate
  2. customevaporated
  3. custompurified by preparative C18 HPLC
  4. washeluting with 10-100% acetonitrile/water
  5. additionSamples containing the product
  6. extractionwere extracted twice with dichloromethane
  7. customthe solvent was evaporated under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-8c91bf875d8d41d19b36e180939ab61e
Quelldatensatz
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08188098B2

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