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

HRID 64173ノート

反応式

HRID 64173 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[CH:48]=[CH:47][C:46]([F:49])=[CH:45][N:44]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[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]([C:43]4[CH:48]=[CH:47][C:46]([F:49])=[CH:45][N:44]=4)=[CH:23][C:18]=3[N:17]=[CH:16]2)[CH:12]=[C:11]([NH:33][S:34]([CH:37]2[CH2:38][CH2:39]2)(=[O:35])=[O:36])[CH:10]=1

参加物

7

反応物 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 27831712-Bromo-5-fluoropyridineHCID 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 117777778N-(2',4'-difluoro-5-(5-(5-fluoropyridin-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamide収率 14.1%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 80711,2-Dimethoxyethane溶媒

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 (0.15 g, 0.272 mmol) in 1,2-dimethoxyethane (5 ml) was degassed by N2 bubbling for 5 min. 2-Bromo-5-fluoropyridine (0.057 g, 0.326 mmol, 1.2 eq.) was added and the mixture was degassed for another 5 min. Pd(dppf)Cl2 (0.011, 0.013 mmol, 0.05 eq.) and aqueous sodium carbonate (0.072, 0.680 mmol, 2.5 eq.) were added and the procedure of Example 1(d) was followed. The crude residue of the product was purified by column chromatography (60-120 silica gel, 80% ethyl acetate in hexane) to yield the title product in 14.1% yield (0.02 g). 1H NMR (400 MHz, DMSO-d6): δ 10.23 (s, 1H), 8.75 (s, 1H), 8.68-8.67 (d, 1H), 8.48 (d, 1H), 8.20-8.13 (m, 2H), 7.86-7.743 (m, 3H), 7.61-7.60 (d, 2H), 7.51-7.43 (m, 2H), 7.30-7.25 (m, 1H), 2.89-2.86 (t, 1H), 1.03-1.02 (d, 4H); LC-MS (ESI): Calculated mass: 520.53; Observed mass: 521.2 [M+H]+ (rt: 1.64 min).

後処理

  1. customthe mixture was degassed for another 5 min
  2. customThe crude residue of the product was purified by column chromatography (60-120 silica gel, 80% ethyl acetate in hexane)

出典と根拠

ORDレコード
ord-cddba55b3e7244ad819db9e858738851
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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