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 406988ノート

反応式

HRID 406988 の反応式
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]

参加物

8

反応物 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

生成物 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-carboxylate収率 34%

試薬・触媒・溶媒 3

HCID 962Water触媒HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-5f1fb5f473d54464bd4c2ae6cfe19c4e
出典データセット
uspto-grants-2014_06
特許番号
US08754114B2

反応ノート

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