Cesium carbonate → 1-[4-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-3-methyl-1,3-dihydro-benzoimidazol-2-ylideneamine

HRID 410337Notes

Reaction equation

HRID 410337 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]([CH3:16])[C:8]2=[NH:17])=[CH:4][CH:3]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[C:66]1([C:79]2[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=2)[CH:71]=[CH:70][CH:69]=[CH:68][C:67]=1[CH2:72][N:73]1[CH2:78][CH2:77][NH:76][CH2:75][CH2:74]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:66]1([C:79]2[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=2)[CH:71]=[CH:70][CH:69]=[CH:68][C:67]=1[CH2:72][N:73]1[CH2:74][CH2:75][N:76]([C:2]2[CH:19]=[CH:18][C:5]([CH2:6][N:7]3[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=4[N:9]([CH3:16])[C:8]3=[NH:17])=[CH:4][CH:3]=2)[CH2:77][CH2:78]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 183819371-Biphenyl-2-ylmethyl-piperazineHCID 585649661-(4-Bromo-benzyl)-3-methyl-1,3-dihydro-benzoimidazol-2-ylideneamine

Product 1

HCID 462416001-[4-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-3-methyl-1,3-dihydro-benzoimidazol-2-ylideneamineYield 12.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
95 °C

Procedure

To a degassed solution of 1-(4-bromo-benzyl)-3-methyl-1,3-dihydro-benzoimidazol-2-ylideneamine (75 mg, 0.237 mmol) in anhydrous toluene (2 ml) was added Pd(OAc)2 (20 mg, 0.047 mmol). Nitrogen was bubbled through the suspension for 10 min before BINAP (29 mg, 0.047 mmol) was added. After a further 2 min 1-biphenyl-2-ylmethyl-piperazine (65 mg, 0.258 mmol) in degassed toluene (2 ml) was introduced and then after a additional 2 min Cs2CO3 (1.54 g, 4.75 mmol) was added and the reaction was stirred for 2 min. Throughout all of the additions nitrogen was continuously bubbled through the reaction mixture. The reaction was then sealed and heated to 95° C. where it was maintained for 16 h. After this time the dark red mixture was cooled to rt and filtered through Celite®. The collected solids were washed with additional toluene and then the combined filtrate and washings were concentrated under reduced pressure to give the crude product. Purification by preparative HPLC provided 1-[4-(4-biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-3-methyl-1,3-dihydro-benzoimidazol-2-ylideneamine as a solid (14 mg, 12%). HPLC-MS 488 [M+1]+, 255.

Workup

  1. additionwas added
  2. customThroughout all of the additions nitrogen was continuously bubbled through the reaction mixture
  3. customThe reaction was then sealed
  4. temperaturewas maintained for 16 h
  5. temperatureAfter this time the dark red mixture was cooled to rt
  6. filtrationfiltered through Celite®
  7. washThe collected solids were washed with additional toluene
  8. concentrationthe combined filtrate and washings were concentrated under reduced pressure
  9. customto give the crude product
  10. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-90f5050666014807aaa3194cc09df6c4
Source dataset
uspto-grants-2014_06
Patent number
US08759520B2

Reaction notes

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