Cesium carbonate → [1-(2-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-ylidene]-carbamic acid tert-butyl ester

HRID 410346Notes

Reaction equation

HRID 410346 reaction equation
[C:1]([O:5][C:6](=[O:36])[N:7]=[C:8]1[N:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2Br)[C:11]2[CH:21]=[CH:22][CH:23]=[CH:24][C:10]=2[N:9]1[CH2:25][CH2:26][CH2:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)([CH3:4])([CH3:3])[CH3:2].[C:37]1([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[CH2:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([O:5][C:6](=[O:36])[N:7]=[C:8]1[N:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N:47]2[CH2:48][CH2:49][N:44]([CH2:43][C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=3[C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[CH2:45][CH2:46]2)[C:11]2[CH:21]=[CH:22][CH:23]=[CH:24][C:10]=2[N:9]1[CH2:25][CH2:26][CH2:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 183819371-Biphenyl-2-ylmethyl-piperazineHCID 76831672[1-(2-Bromo-benzyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-ylidene]-carbamic acid tert-butyl ester

Product 1

HCID 67428842[1-(2-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-ylidene]-carbamic acid tert-butyl esterYield 38.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Procedure

To a degassed solution of [1-(2-bromo-benzyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-ylidene]-carbamic acid tert-butyl ester (200 mg, 0.36 mmol) in anhydrous toluene (4 ml) was added Pd(OAc)2 (0.7 mg, 1.8 □mol). Nitrogen was bubbled through the suspension for 10 min before BINAP (17 mg, 27 □mol) was added. After a further 2 min 1-biphenyl-2-ylmethyl-piperazine (99 mg, 0.36 mmol) in degassed toluene (4 ml) was introduced and then after a additional 2 min Cs2CO3 (0.86 g, 2.6 mmol) was added and the reaction was stirred for 2 min. Throughout all of the additions nitrogen was continuously bubbled through the reaction mixture. To After 2.75 h the reaction was cooled to rt and filtered through Celite®. Purification by chromatography on silica gave [1-[2-(4-biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-ylidene]-carbamic acid tert-butyl ester (100 mg) which was used without purification in the next step.

Workup

  1. customNitrogen was bubbled through the suspension for 10 min before BINAP (17 mg, 27 □mol)
  2. additionwas added
  3. customThroughout all of the additions nitrogen was continuously bubbled through the reaction mixture
  4. filtrationfiltered through Celite®
  5. customPurification by chromatography on silica

Sources & evidence

ORD record
ord-1586cb5ed01e49beb21f4a1c63f2d67c
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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