Cesium carbonate → HCID 67403049, compound

HRID 913908Notes

Reaction equation

HRID 913908 reaction equation
Br[C:2]1[CH:36]=[CH:35][C:5]2[N:6]([CH2:31][CH:32]3[CH2:34][CH2:33]3)[C:7]([CH2:9][O:10][CH2:11][C:12]3([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)=[N:8][C:4]=2[CH:3]=1.[C:37]([C:39]1[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=1)#[N:38].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Pd]>[C:37]([C:39]1[CH:44]=[CH:43][C:42]([C:2]2[CH:36]=[CH:35][C:5]3[N:6]([CH2:31][CH:32]4[CH2:33][CH2:34]4)[C:7]([CH2:9][O:10][CH2:11][C:12]4([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:14][CH2:13]4)=[N:8][C:4]=3[CH:3]=2)=[CH:41][CH:40]=1)#[N:38]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343264-Cyanophenylboronic acidHCID 57546192HCID 57546192, compound

Product 1

HCID 67403049HCID 67403049, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 1140TolueneSolvent

Procedure

Following the procedure is described in the literature (Lee, S. H. et. al. J. Org. Chem. 2004, 69, 8829-8835). tert-Butyl 4-(((5-bromo-1-(cyclopropylmethyl)-1H-benzo-[d]imidazol-2-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (48 mg, 0.087 mmol) was subjected to Suzuki coupling reaction in toluene (1.0 mL) at 110° C. with p-cyanophenylboronic acid (3 equiv) and cesium carbonate (3 equiv) using Pd (dppf) (0.08 equiv) as catalyst. The crude product was purified by silica gel chromatography using a 50 min linear gradient of 12% -100% ethyl acetate in hexane. Fractions containing the required product were combined and evaporated in vacuo to give 23 mg (46%) as a gum. 1H-NMR (CD3OD, 500 MHz) δ 7.91 (s, 1H), 7.85 (d, JAB=8.5 Hz, 2H), 7.80 (d, JAB=8.5 Hz, 2H), 7.65-7.60 (m, 2H), 7.36-7.29 (m, 4H), 7.21 (m, 1H), 4.71 (s, 2H), 3.82, (d, J=7.0 Hz, 2H), 3.72 (m, 2H), 3.58 (s, 2H), 3.04 (m, 2H), 2.20 (m, 2H), 1.84 (m, 2H), 1.42 (s, 9H), 1.04 (m, 1H), 0.50-0.47 (m, 2H), 0.33-0.30 (m, 2H); 13C NMR (CD3OD, 126 MHz,) δ 155.7, 151.9, 146.5, 143.1, 142.2, 136.2, 134.3, 132.8, 128.5, 128.0, 127.3, 126.4, 122.9, 118.9, 117.6, 111.6, 110.4, 80.0, 79.9, 65.6, 41.6, 32.1, 27.7, 11.0, 3.6. Mass Spec.: 577(MH)+.

Workup

  1. customThe crude product was purified by silica gel chromatography
  2. additionFractions containing the required product
  3. customevaporated in vacuo
  4. customto give 23 mg (46%) as a gum

Sources & evidence

ORD record
ord-3183f88e74fe4b7eb90b2312a4783184
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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