1,2-Dimethoxyethane → 4-{4-[6-Amino-5-(3-methylbenzofuran-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1926329

Reaktionsgleichung

Reaktionsgleichung von HRID 1926329
COCCOC.[CH3:7][C:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[O:10][C:9]=1B1OC(C)(C)C(C)(C)O1.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([N:39]2[CH:43]=[C:42]([C:44]3[CH:45]=[N:46][C:47]([NH2:51])=[C:48](Br)[CH:49]=3)[CH:41]=[N:40]2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27].C(=O)([O-])[O-].[K+].[K+]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.C(Cl)Cl.O>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([N:39]2[CH:43]=[C:42]([C:44]3[CH:45]=[N:46][C:47]([NH2:51])=[C:48]([C:9]4[O:10][C:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=5[C:8]=4[CH3:7])[CH:49]=3)[CH:41]=[N:40]2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

Komponenten

8

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 591330904,4,5,5-Tetramethyl-2-(3-methylbenzofuran-2-yl)-1,3,2-dioxaborolaneHCID 67366272tert-butyl 4-(4-(6-amino-5-bromopyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Produkt 1

HCID 675209944-{4-[6-Amino-5-(3-methylbenzofuran-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 18456801dichloropalladium DCMKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To the DME solution of 3-methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzofuran (2.3 mL, 0.58 mmol, 2 eq.) from the previous step were added 4-[4-(6-amino-5-bromopyridin-3-yl)-pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl ester (BB3) (120 mg, 0.29 mmol, 1 eq.), potassium carbonate (120 mg, 0.87 mmol, 3 eq.), water (0.5 mL), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium DCM (10 mg, 0.01 mmol, 0.05 eq.). The mixture was evacuated and filled with nitrogen (3×) and heated in a microwave reactor to 100° C. for 30 min. The crude was passed through Thiol-SPE to remove Pd. The clear solution was purified with the MDPS. 1H NMR (400 MHz, CD3OD): δ=1.48 (s, 9H), 1.96 (dq, J=4.3, 12.3 Hz, 2H), 2.09 (br. s., 2H), 2.35 (s, 3H), 2.96 (br. s., 2H), 4.21 (br. s., 2H), 4.33-4.43 (m, 1H), 7.29 (dt, J=0.8, 7.4 Hz, 1H), 7.34 (dt, J=1.4, 7.2 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 7.59-7.65 (m, 1H), 7.82 (s, 1H), 7.85 (d, J=2.3 Hz, 1H), 8.07 (s, 1H), 8.26 (d, J=2.3 Hz, 1H). MS (ES+): m/z=474.38 (100) [MH+]. HPLC: tR=0.94 min (UPLC-ACQUITY, Analytical).

Aufarbeitung

  1. customThe mixture was evacuated
  2. additionfilled with nitrogen (3×)
  3. customto remove Pd
  4. customThe clear solution was purified with the MDPS

Quellen und Nachweise

ORD-Eintrag
ord-bad2adfddd584cbfb7ba6c046dac4189
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08178668B2

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