Nitrogen → N-(5-(5-(3-amino-1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamide

HRID 64190Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 64190
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([N:15]2[C:19]3[CH:20]=[CH:21][C:22](B4OC(C)(C)C(C)(C)O4)=[CH:23][C:18]=3[N:17]=[CH:16]2)[CH:12]=[C:11]([NH:33][S:34]([CH:37]2[CH2:39][CH2:38]2)(=[O:36])=[O:35])[CH:10]=1.N#N.Br[C:43]1[C:44]([NH2:49])=[N:45][N:46]([CH3:48])[CH:47]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.CCO.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[NH2:49][C:44]1[C:43]([C:22]2[CH:21]=[CH:20][C:19]3[N:15]([C:13]4[CH:12]=[C:11]([NH:33][S:34]([CH:37]5[CH2:39][CH2:38]5)(=[O:35])=[O:36])[CH:10]=[C:9]([C:3]5[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=5[F:1])[CH:14]=4)[CH:16]=[N:17][C:18]=3[CH:23]=2)=[CH:47][N:46]([CH3:48])[N:45]=1

Komponenten

7

Edukt 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 27352834-bromo-1-methyl-1H-pyrazol-3-amineHCID 89501185N-(2',4'-difluoro-5-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamide

Produkt 1

HCID 117777783N-(5-(5-(3-amino-1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamideAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 18504229Ethanol tetrahydrofuran waterLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A solution of N-(2′,4′-difluoro-5-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1′-biphenyl]-3-yl)cyclopropanesulfonamide (100 mg, 0.181 mmol) in THF/EtOH/Water (5:5:2) was degassed by N2 bubbling for 5 min. 4-Bromo-1-methyl-1H-pyrazol-3-amine (35 mg, 0.19 mmol, 1.1 eq.) was added and the mixture was degassed for another 5 min. Bis(tri-tert-butylphosphine)palladium(0) (5 mg, 0.009 mmol, 0.05 eq.) and cesium carbonate (170 mg, 0.54 mmol, 3.0 eq.) were added sequentially and the mixture was further degassed for 5 min and heated at 90° C. for 16 h. The mixture was quenched and extracted as in Example 1(d). The solvent was distilled off to give the crude residue which was purified by preparative HPLC to give the product in 27% yield (25 mg). 1H NMR (300 MHz, DMSO): δ 10.3 (s, 1H) 8.79 (s, 1H), 7.95-7.92 (m, 2H), 7.77-7.07 (m, 2H), 7.59 (s, 2H), 7.53-7.47 (m, 3H), 7.29 (m, 1H), 3.75 (s, 3H), 2.91 (m, 1H), 1.5-1.49 (d, 2H), 1.30-1.26 (t, 2H), 1.03-1.01 (t, 2H); LC-MS (ESI): Calculated mass: 520.5; Observed mass: 521.0 [M+H]+ (rt: 0.676 min).

Aufarbeitung

  1. customthe mixture was degassed for another 5 min
  2. customthe mixture was further degassed for 5 min
  3. customThe mixture was quenched
  4. extractionextracted as in Example 1(d)
  5. distillationThe solvent was distilled off

Quellen und Nachweise

ORD-Eintrag
ord-7ba68167e82d4bb580f0822aee4d4938
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447091B2

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