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Binap, (A+-)- → 1,1-Dimethylethyl 4-(6-chloro-4-fluoro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

HRID 447760
Notes
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Reaction equation

HRID 447760 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([F:9])[C:3]=1[NH:10][C:11]([NH:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)=[O:12].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>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].O1CCOCC1>[Cl:8][C:6]1[CH:5]=[C:4]([F:9])[C:3]2[NH:10][C:11](=[O:12])[N:13]([CH:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[C:2]=2[CH:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 634876Binap, (A+-)-HCID 596832771,1-Dimethylethyl 4-({[(2-bromo-4-chloro-6-fluorophenyl)amino]-carbonyl}amino)-1-piperidinecarboxylate

Product 1

HCID 596832761,1-Dimethylethyl 4-(6-chloro-4-fluoro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Under an argon atmosphere, 1,1-dimethylethyl 4-({[(2-bromo-4-chloro-6 fluorophenyl)amino]carbonyl}amino)-1-piperidinecarboxylate (D7) (1.09 mmol, 0.493 g), 1,4-dioxane (4.4 ml), Pd2 dba3 (0.05 eq., 0.054 mmol, 50 mg), BINAP (0.055 eq., 0.059 mmol, 37 mg), NatBuO (1.5 eq., 1.63 mmol, 157 mg) were mixed together and heated to 80° C. under argon for 4 days. The reaction mixture was cooled to room temperature, quenched with water and the aqueous solution obtained was extracted with ethyl acetate. The solvent was evaporated and the crude was purified by MDAP. Fractions were collected and the solvent evaporated to yield the title compound, 15 mg, 3%, M+-H=368.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with water
  3. customthe aqueous solution obtained
  4. extractionwas extracted with ethyl acetate
  5. customThe solvent was evaporated
  6. customthe crude was purified by MDAP
  7. customFractions were collected
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-9c5bc89a15ee49d6b932fce5d641b7ca
Source dataset
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08481566B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes