2-Pyridinemethanamine → HCID 24954097, compound

HRID 1801596Notes

Reaction equation

HRID 1801596 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH2:8].Br[C:10]1[CH:11]=[C:12]([CH:23]=[CH:24][C:25]=1[Cl:26])[CH2:13][NH:14][C@@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16].CC([O-])(C)C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)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].C1(C)C=CC=CC=1>[Cl:26][C:25]1[CH:10]=[CH:11][C:12]([CH2:13][NH:14][C@@H:15]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH3:16])=[CH:23][C:24]=1[NH:8][CH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1

Participants

7

Reactant 4

HCID 195092-PyridinemethanamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 59803176HCID 59803176, compound

Product 1

HCID 24954097HCID 24954097, compoundYield 12.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of pyridin-2-ylmethanamine (0.105 g, 1.0 mmol) and (R)—N-(3-bromo-4-chlorobenzyl)-1-phenylethanamine 73 (0.251 g, 0.8 mmol) was added sodium 2-methylpropan-2-olate (0.103 g, 1 mmol), Pd2(dba)3 (0.051 g, 0.06 mmol), 2-(diphenylphosphino)-1-(2-(diphenylphosphino)naphthalen-1-yl)naphthalene (0.210 mg, 0.34 mmol), and toluene (1.5 mL). The reaction mixture was degassed by bubbling nitrogen through the solution for 15 min and heated to 80° C. After 20 h, the reaction mixture was diluted with EtOAc and saturated NaHCO3. The organic phase was washed with brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 60% to 100% EtOAc in hexanes) followed by flash column chromatography on silica gel (eluted with 1% to 5% MeOH (2 M in NH3) in DCM) gave (R)-2-chloro-5-((1-phenylethylamino)methyl)-N-(pyridin-2-ylmethyl)benzenamine 74 (0.034 g, 12% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.31 (d, J=6.5 Hz, 3H), 3.46 (d, J=13.3 Hz, 1H), 3.55 (d, J=13.3 Hz, 1H), 3.72 (q, J=6.5 Hz, 1H), 4.53 (d, J=5.5 Hz, 2H), 5.38 (m, 1H), 6.54-6.58 (m, 2H), 7.20-7.33 (m, 9H), 7.66 (td, J=7.6, 1.8 Hz, 1H), 8.62 (d, J=4.3 Hz, 1H). Mass spectrum: calculated for C21H22ClN3 351.2. found 352.2 (M++1).

Workup

  1. customThe reaction mixture was degassed
  2. customby bubbling nitrogen through the solution for 15 min
  3. additionthe reaction mixture was diluted with EtOAc and saturated NaHCO3
  4. washThe organic phase was washed with brine (1×)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash column chromatography on silica gel (eluted with 60% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-893aaadff3f14aa9922a75684b180f47
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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