Dichloromethane → tert-butyl 4-(4-{1-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]-1H-benzimidazol-5-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 406988노트

반응식

HRID 406988 반응식
Br[C:2]1[CH:25]=[CH:24][C:5]2[N:6]([C:9]3[CH:10]=[C:11]([NH:15][C:16]([NH:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[O:17])[CH:12]=[CH:13][CH:14]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[N:36][N:37]([CH:39]3[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH2:40]3)[CH:38]=2)O1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:21][C:20]([F:23])([F:22])[CH2:19][NH:18][C:16]([NH:15][C:11]1[CH:10]=[C:9]([N:6]2[C:5]3[CH:24]=[CH:25][C:2]([C:34]4[CH:35]=[N:36][N:37]([CH:39]5[CH2:40][CH2:41][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:43][CH2:44]5)[CH:38]=4)=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH:14]=[CH:13][CH:12]=1)=[O:17]

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 67980496N-[3-(5-bromo-1H-benzimidazol-1-yl)phenyl]-N'-(2,2,2-trifluoro ethyl)urea

생성물 1

HCID 67980276tert-butyl 4-(4-{1-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]-1H-benzimidazol-5-yl}-1H-pyrazol-1-yl)piperidine-1-carboxylate수율 34%

시약·촉매·용매 3

HCID 962Water촉매HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매

실험 절차

The mixture of N-[3-(5-bromo-1H-benzimidazol-1-yl)phenyl]-N′-(2,2,2-trifluoroethyl)urea (1.0000 g, 2.4202 mmol) (prepared from the procedure of Example 1, step 4), tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate (1.1 g, 2.8 mmol), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (1:1) (0.1 g, 0.1 mmol, Aldrich, Cat. No. 697360) and sodium carbonate (510 mg, 4.8 mmol) in 1,4-dioxane (10 mL) and a few drops of water was heated at 120° C. under nitrogen overnight. After the reaction mixture was cooled to r.t, it was filtered, and the solid was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on a silica gel column using 6% MeOH CH2Cl2 as eluent to afford the desired compound (0.48 g, 34%). LCMS (M+H)+: m/z=584.2.

후처리

  1. temperatureAfter the reaction mixture was cooled
  2. filtrationit was filtered
  3. washthe solid was washed with ethyl acetate
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography on a silica gel column

출처 및 근거

ORD 기록
ord-5f1fb5f473d54464bd4c2ae6cfe19c4e
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754114B2

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