Binap, (A+-)- → HCID 67011716, compound

HRID 2111807Notes

Reaction equation

HRID 2111807 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([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:4][CH:3]=1.Cl.[O:28]([CH2:35][CH2:36][CH2:37][NH2:38])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=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(O[Na])(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:28]([CH2:35][CH2:36][CH2:37][NH:38][C:2]1[CH:7]=[CH:6][C:5]([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:4][CH:3]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 634876Binap, (A+-)-HCID 18590545(3-Aminopropoxy)benzene hydrochlorideHCID 69066394HCID 69066394, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 67011716HCID 67011716, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A flask containing 1-(4-bromophenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide (EXAMPLE C2, 100 mg, 0.25 mmol) and 3-phenoxypropylamine hydrochloride (54 mg, 0.29 mmol) was evacuated and refilled with N2 (2×). To this was added BINAP (112 mg, 0.18 mmol), Pd2 dba3 (55 mg, 0.06 mmol) and t-BuONa (68 mg, 0.7 mmol) in one portion as a mixture, with minimum exposure to air. The flask was again evacuated and refilled with N2 (3×). Degassed, anhydrous dioxane (2 mL) was added via syringe and the solution was stirred under N2 for 10 min at rt and then at 80° C. for 18 h. Later, the reaction was cooled to rt, filtered through Celite (using MeOH and CH2Cl2 to rinse the Celite), concentrated under reduced pressure and purified using the Waters mass-directed HPLC purification system to provide 1-{4-[(3-phenoxypropyl)amino]phenyl}-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide as a white solid. MS (ES+): m/z 478 (100) [MH+].

Workup

  1. customwas evacuated
  2. additionrefilled with N2 (2×)
  3. customThe flask was again evacuated
  4. additionrefilled with N2 (3×)
  5. customDegassed
  6. additionanhydrous dioxane (2 mL) was added via syringe
  7. waitat 80° C. for 18 h
  8. temperatureLater, the reaction was cooled to rt
  9. filtrationfiltered through Celite (
  10. washto rinse the Celite),
  11. concentrationconcentrated under reduced pressure
  12. custompurified
  13. customthe Waters mass-directed HPLC purification system

Sources & evidence

ORD record
ord-e346c8c2edba4aaba403d78401e9b7b5
Source dataset
uspto-grants-2009_04
Patent number
US07521448B2

Reaction notes

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