4-Cyanophenylboronic acid → 1-(4'-cyano-1,1'-biphenyl-3-yl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide

HRID 28665

Reaction equation

HRID 28665 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([C:17]([NH:19][CH2:20][C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)=[O:18])=[CH:16][C:11]=3[N:10]=[CH:9]2)[CH:5]=[CH:6][CH:7]=1.[C:27]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)#[N:28]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([C:29]1[CH:34]=[CH:33][C:32]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([N:8]3[C:12]4[CH:13]=[CH:14][C:15]([C:17]([NH:19][CH2:20][C:21]5[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=5)=[O:18])=[CH:16][C:11]=4[N:10]=[CH:9]3)[CH:3]=2)=[CH:31][CH:30]=1)#[N:28]

Participants

4

Reactant 2

HCID 27343264-Cyanophenylboronic acidHCID 576397171-(3-bromophenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide

Product 1

HCID 116976501-(4'-cyano-1,1'-biphenyl-3-yl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamideYield 22%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A flask containing a mixture of 1-(3-bromophenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide (prepared according to the general procedures described above, 80 mg, 0.20 mmol) and 4-cyanophenylboronic acid (57 mg, 0.39 mmol) was evacuated and refilled with N2 (2×). To this was added Pd(PPh3)4 (34 mg, 0.029 mmol) in one portion with minimum exposure to air. The flask was again evacuated and refilled with N2 (3×). Degassed solutions of DME-EtOH (4:1 v/v, 2 mL) and aq Na2CO3 (2M, 0.6 mL) were added via syringe and the solution was stirred under N2 for 10 min at rt and then at 85° C. for 19 h. The reaction was then cooled to rt, filtered, and purified using the Waters mass-directed HPLC purification system. Further recrystallization from acetonitrile yielded 1-(4′-cyano-1,1′-biphenyl-3-yl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide as a white solid (18.5 mg, 22% yield). MS (ES+): m/z430 (100) [MH+]. 1H NMR (400 MHz, CD3OD): δ=8.66 (s, 1H), 8.61 (d, J=2.4Hz, 1H), 8.45 (dd, J=4.8 Hz, 1.2 Hz, 1H), 8.34 (dd, J=1.0 Hz, 0.4 Hz, 1H), 7.99 (t, J=1.6 Hz, 1H), 7.88-7.86 (m, 3H), 7.86-7.82 (m, 4H), 7.80 (t, J=8.0 Hz, 1H), 7.74 (d, J=8.8 Hz, 2H), 7.43 (dd, J=8.4 Hz, 5.2 Hz, 1H), 7.67 (s, 2H).

Workup

  1. additionA flask containing
  2. customprepared
  3. customwas evacuated
  4. additionrefilled with N2 (2×)
  5. customThe flask was again evacuated
  6. additionrefilled with N2 (3×)
  7. additionDegassed solutions of DME-EtOH (4:1 v/v, 2 mL) and aq Na2CO3 (2M, 0.6 mL) were added via syringe
  8. waitat 85° C. for 19 h
  9. temperatureThe reaction was then cooled to rt
  10. filtrationfiltered
  11. custompurified
  12. customthe Waters mass-directed HPLC purification system
  13. customFurther recrystallization from acetonitrile

Sources & evidence

ORD record
ord-0c0fe40783bc4d9ca32b0d6c75bc77d8
Source dataset
uspto-grants-2008_09
Patent number
US07419995B2

Linked notes

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