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

HRID 64172노트

반응식

HRID 64172 반응식
[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[S:44][C:45]([CH3:48])=[N:46][N:47]=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[S:44][C:45]([CH3:48])=[N:46][N:47]=4)=[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

참가 물질

7

반응물 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 71719042-Bromo-5-methyl-1,3,4-thiadiazoleHCID 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

생성물 1

HCID 89501271N-(2',4'-difluoro-5-(5-(5-methyl-1,3,4-thiadiazol-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamide수율 4.2%

시약·촉매·용매 2

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

실험 절차

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-methyl-1,3,4-thiadiazole (0.058 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 desired title product in 4.2% yield (0.006 g). 1H NMR (400 MHz, DMSO-d6): δ 10.21 (s, 1H), 8.81 (s, 1H), 8.34-8.33 (s, 1H), 8.00-7.98 (dd, 1H), 7.84 (d, 1H), 7.79-7.73 (m, 1H), 7.54 (s, 1H), 7.49-7.42 (m, 2H), 7.29-7.24 (m, 1H), 3.17-3.16 (d, 2H), 2.85-2.84 (m, 1H), 2.79 (s, 3H), 1.01-0.99 (m, 4H); LC-MS (ESI): Calculated mass: 523.58; Observed mass: 523.7 [M+H]+ (rt: 1.50 min).

후처리

  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)

출처 및 근거

ORD 기록
ord-61ee90b3e1684de3a9e1bb0ba1896f0e
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447091B2

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