Sodium Carbonate → N2-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide

HRID 897832Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 897832
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][CH2:13][OH:14])[N:9]=[C:10](I)[C:3]=12.[CH3:15][O:16][C:17]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[CH:19][C:18]=1[NH:32][C:33]([C:35]1[N:36]([CH3:44])[C:37]2[C:42]([CH:43]=1)=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:34].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][CH2:13][OH:14])[N:9]=[C:10]([C:21]3[CH:20]=[CH:19][C:18]([NH:32][C:33]([C:35]4[N:36]([CH3:44])[C:37]5[C:42]([CH:43]=4)=[CH:41][CH:40]=[CH:39][CH:38]=5)=[O:34])=[C:17]([O:16][CH3:15])[CH:22]=3)[C:3]=12

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 22346783HCID 22346783, Verbindung2×HCID 22347095N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide

Produkt 1

HCID 22346971N2-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamideAusbeute 84 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A mixture of 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-ethanol (Intermediate 3) (0.364 g, 1.19 mol), N2-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-2-indolecarboxamide (0.485 g, 1.19 mmol), palladium tetrakis(triphenylphosphine) (0.138 g, 0.119 mmol), and sodium carbonate (0.303 g, 2.86 mmol) in DME (12 mL) and water (12 mL) was heated at 85° C. for 4 h then cooled to ambient temperature. The DME was removed in vacuo and the resulting precipitate was collected by filtration and rinsed with water (50 mL) and ether (50 mL) to afford N2-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide as a tan solid (0.459 g, 1.00 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.44 (1H, s), 8.26 (1H, s), 8.12 (1H, d, J=8.0 Hz), 7.70 (1H, d, J=8.0 Hz), 7.59 (1H, d, J=8.4 Hz), 7.29-7.41 (6H, m), 7.15 (1H, t, J=7.4 Hz), 4.90 (1H, t, J=5.8 Hz), 4.41 (2H, t, J=5.8 Hz), 4.04 (3H, s), 3.96 (3H, s), and 3.86 (2H, q, J=5.9 Hz); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile-0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 10.52 min.

Aufarbeitung

  1. temperaturethen cooled to ambient temperature
  2. customThe DME was removed in vacuo
  3. filtrationthe resulting precipitate was collected by filtration
  4. washrinsed with water (50 mL) and ether (50 mL)

Quellen und Nachweise

ORD-Eintrag
ord-856df9964a1a4cb5b44aa23b7ffe7e70
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06921763B2

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