2-Chloro-5-(trifluoromethyl)pyridine → HCID 67208035, compound

HRID 2041754Notes

Reaction equation

HRID 2041754 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=1.[C:12]([N:15]1[C:24]2[C:19](=[CH:20][C:21]([C:25]3[CH:30]=[CH:29][C:28]([CH2:31][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)=[CH:27][CH:26]=3)=[CH:22][CH:23]=2)[C@H:18]([NH2:38])[CH2:17][C@@H:16]1[CH3:39])(=[O:14])[CH3:13].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-:89])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:12]([OH:14])=[O:89].[C:12]([N:15]1[C:24]2[C:19](=[CH:20][C:21]([C:25]3[CH:30]=[CH:29][C:28]([CH2:31][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)=[CH:27][CH:26]=3)=[CH:22][CH:23]=2)[C@H:18]([NH:38][C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=2)[CH2:17][C@@H:16]1[CH3:39])(=[O:14])[CH3:13]

Participants

7

Reactant 4

HCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 67195867HCID 67195867, compound

Product 1

HCID 67208035HCID 67208035, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A flask was charged with 2-chloro-5-(trifluoromethyl)pyridine (57.7 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-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-N-[5-(trifluoromethyl)-2-pyridinyl]-1,2,3,4-tetrahydro-4-quinolinamine formate salt (15 mg, 0.026 mmol, 10%) 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-4f5f842bd37d443b9536f794f4b7ca07
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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