2-Chloropyridine → HCID 68162252, compound

HRID 2041753Notes

Reaction equation

HRID 2041753 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].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.CC(C)([O-:78])C.[Na+].Cl[C:82]1[CH:87]=[CH:86][CH:85]=[CH:84][N:83]=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]>[CH:1]([OH:3])=[O:78].[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:82]2[CH:87]=[CH:86][CH:85]=[CH:84][N:83]=2)[CH2:6][C@@H:5]1[CH3:28])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 79772-ChloropyridineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 67195867HCID 67195867, compound

Product 1

HCID 68162252HCID 68162252, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

(cis)-1-Acetyl-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation see intermediate 25) (100 mg, 0.265 mmol), racemic BINAP (8.25 mg, 0.013 mmol), sodium tert-butoxide (30.5 mg, 0.318 mmol), 2-chloropyridine (0.025 ml, 0.265 mmol) and tris(dibenzylideneacetone)dipalladium(0) (12.13 mg, 0.013 mmol) were suspended in toluene (2.5 mL) under nitrogen and the resulting mixture was stirred at 100° C. for 5 h under microwave irradiation then cooled to room temperature and partitioned between AcOEt (20 mL) and 1:1 saturated NaHCO3 aqueous solution:water (5 mL). The layers were separated and the organic phase washed with saturated NaHCO3 aqueous solution:water (5 mL) then brine (5 mL), dried over Na2SO4 and concentrated in vacuo. Purification of the residue by MDAP (modifier: formic acid) gave (cis)-1-acetyl-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-N-2-pyridinyl-1,2,3,4-tetrahydro-4-quinolinamine formate salt (31.9 mg, 0.062 mmol, 24%) as a white solid.

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between AcOEt (20 mL) and 1:1 saturated NaHCO3 aqueous solution
  3. customThe layers were separated
  4. washthe organic phase washed with saturated NaHCO3 aqueous solution
  5. dry with materialwater (5 mL) then brine (5 mL), dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by MDAP (modifier: formic acid)

Sources & evidence

ORD record
ord-204e63f9aa4e4e8caeb2a287207dc1a5
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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