2,5-Dichloropyridine → HCID 68161475, compound

HRID 2041756Notes

Reaction equation

HRID 2041756 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.[C:9]([N:12]1[C:21]2[C:16](=[CH:17][C:18]([C:22]3[CH:27]=[CH:26][C:25]([CH2:28][N:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)=[CH:24][CH:23]=3)=[CH:19][CH:20]=2)[C@H:15]([NH2:35])[CH2:14][C@@H:13]1[CH3:36])(=[O:11])[CH3:10].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-:86])C.[Na+]>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].C1(C)C=CC=CC=1>[CH:9]([OH:11])=[O:86].[C:9]([N:12]1[C:21]2[C:16](=[CH:17][C:18]([C:22]3[CH:27]=[CH:26][C:25]([CH2:28][N:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)=[CH:24][CH:23]=3)=[CH:19][CH:20]=2)[C@H:15]([NH:35][C:2]2[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=2)[CH2:14][C@@H:13]1[CH3:36])(=[O:11])[CH3:10]

Participants

7

Reactant 4

HCID 276852,5-DichloropyridineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 67195867HCID 67195867, compound

Product 1

HCID 68161475HCID 68161475, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A flask was charged with 2-chloro-5-chloropyridine (47.0 mg, 0.318 mmol), (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) and tris(dibenzylideneacetone)dipalladium(0) (12.13 mg, 0.013 mmol) then filled with toluene (2.5 mL), and the resulting mixture was stirred at 110° C. under nitrogen for 16 h then cooled to room temperature and loaded on a 5 g SCX cartridge. It was then eluted with MeOH (30 mL) followed by 2M NH3 in MeOH (25 mL). The ammonia fractions were collected and concentrated in vacuo. Purification of the residue by MDAP (modifier: formic acid) gave (cis)-1-acetyl-N-(5-chloro-2-pyridinyl)-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-1,2,3,4-tetrahydro-4-quinolinamine formate salt (23 mg, 0.04 mmol, 15%) as an off white solid.

Workup

  1. temperaturethen cooled to room temperature
  2. washIt was then eluted with MeOH (30 mL)
  3. customThe ammonia fractions were collected
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by MDAP (modifier: formic acid)

Sources & evidence

ORD record
ord-60af372c2f44454699c6971d278788b9
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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