Binap, (A+-)- → HCID 67207541, compound

HRID 2041763Notes

Reaction equation

HRID 2041763 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:27])[CH2:6][C@@H:5]1[CH3:28])(=[O:3])[CH3:2].Cl[C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][N:31]=1.CC(C)([O-])C.[Na+].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>C1(C)C=CC=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]>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:27][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][N:31]=2)[CH2:6][C@@H:5]1[CH3:28])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 27828012-Chloro-5-fluoropyridineHCID 23676156Sodium t-butoxideHCID 67195867HCID 67195867, compound

Product 1

HCID 67207541HCID 67207541, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (2S,4R)-1-acetyl-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation see intermediate 66) (150 mg, 0.397 mmol) in toluene (4 mL) was treated under nitrogen with 2-chloro-5-Fluoropyridine (63 mg, 0.479 mmol), sodium tert-butoxide (46 mg, 0.479 mmol), racemic BINAP (12.9 mg, 0.021 mmol) and tris(dibenzylideneacetone)dipalladium(0) (19 mg, 0.021 mmol) and the resulting mixture was stirred under nitrogen at 110° C. for 16 h then cooled to room temperature. The mixture was loaded on a 5 g SCX cartridge and eluted with MeOH (25 mL) then with a 2N NH3 in MeOH (25 mL). The ammonia fractions were combined and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel using a 20 G silica cartridge (gradient:1 to 5% (2N NH3 in MeOH) in DCM) gave (2S,4R)-1-acetyl-N-(5-fluoro-2-pyridinyl)-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-1,2,3,4-tetrahydro-4-quinolinamine (49.7 mg, 0.098 mmol, 25%) as an orange oil.

Workup

  1. temperaturethen cooled to room temperature
  2. washeluted with MeOH (25 mL)
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by flash chromatography on silica gel using a 20 G silica cartridge (gradient:1 to 5% (2N NH3 in MeOH) in DCM)

Sources & evidence

ORD record
ord-86c6bc63f5cc47c1991ea85edaefaa91
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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