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 64190ノート

反応式

HRID 64190 の反応式
[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

参加物

7

反応物 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

生成物 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)cyclopropanesulfonamide収率 27%

試薬・触媒・溶媒 2

HCID 178418851HCID 178418851、化合物触媒HCID 18504229Ethanol tetrahydrofuran water溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-7ba68167e82d4bb580f0822aee4d4938
出典データセット
uspto-grants-2016_09
特許番号
US09447091B2

反応ノート

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