Cesium carbonate → HCID 67520633, Verbindung

HRID 1926267Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1926267
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23](B4OC(C)(C)C(C)(C)O4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:35][C:36]1[C:45]([F:46])=[CH:44][C:43]([F:47])=[C:42]2[C:37]=1[CH:38]=[C:39](OS(C(F)(F)F)(=O)=O)[N:40]=[CH:41]2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23]([C:39]4[N:40]=[CH:41][C:42]5[C:37]([CH:38]=4)=[C:36]([Cl:35])[C:45]([F:46])=[CH:44][C:43]=5[F:47])[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 534879604-[4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-3-yl]pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl esterHCID 86633145HCID 86633145, Verbindung

Produkt 1

HCID 67520633HCID 67520633, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 4-{4-[6-amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB3) (18.3 mg, 0.0391 mmol), trifluoromethanesulfonic acid 5-chloro-6,8-difluoroisoquinolin-3-yl ester (0.0326 mmol), and Pd(PPh3)4 (2.51 mg, 0.00215 mmol) in 1,4-dioxane (0.90 ml) in a sealable microwave tube was added a solution of Cs2CO3 (21.4 mg, 0.0651 mmol) in H2O (0.30 ml). The tube was sealed, evacuated and refilled with nitrogen (3×), and heated in the microwave reactor to 100° C. for 30 min. The reaction mixture was diluted with EtOAc (40 ml), washed with water (2×20 ml) and brine (20 ml), and dried over MgSO4. After concentration in vacuo, a brown oil was obtained. It was then purified by prep. TLC eluting with 4% MeOH/CH2Cl2 to give the title compound as a brown oil. 1H NMR (400 MHz, CDCl3): δ=1.49 (s, 9H), 1.94-2.05 (m, 2H), 2.16-2.24 (m, 2H), 2.87-2.98 (m, 2H), 4.24-4.38 (m, 3H), 6.45 (brs, 2H), 7.18 (t, J=9.6 Hz, 1H), 7.68 (d, J=0.8 Hz, 1H), 7.79 (d, J=0.8 Hz, 1H), 7.99 (d, J=2.4 Hz, 1H), 8.32 (d, J=2.4 Hz, 1H), 8.34 (m, 1H), 9.53 (d, J=1.2 Hz, 1H). MS(ES+): m/z=540.92/542.87 (100/86) [MH+]. HPLC: tR=3.15 min (ZQ3, polar—5 min).

Aufarbeitung

  1. customThe tube was sealed
  2. customevacuated
  3. additionrefilled with nitrogen (3×)
  4. additionThe reaction mixture was diluted with EtOAc (40 ml)
  5. washwashed with water (2×20 ml) and brine (20 ml)
  6. dry with materialdried over MgSO4
  7. concentrationAfter concentration in vacuo
  8. customa brown oil was obtained
  9. customIt was then purified by prep

Quellen und Nachweise

ORD-Eintrag
ord-ad2f580717584504855a96677ec22bfb
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08178668B2

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