3-Pyridinemethanamine → 6-(2-cyanophenyl)-4-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamide

HRID 2074437Notes

Reaction equation

HRID 2074437 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:19]=[C:18]([NH:20][CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=2)[C:12]([C:13](OCC)=[O:14])=[CH:11][N:10]=1)#[N:2].[NH2:30][CH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1.C[Al](C)C>C1(C)C=CC=CC=1>[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:19]=[C:18]([NH:20][CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=2)[C:12]([C:13]([NH:30][CH2:31][C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)=[O:14])=[CH:11][N:10]=1)#[N:2]

Participants

5

Reactant 3

HCID 310183-PyridinemethanamineHCID 16682925TrimethylaluminumHCID 59744986Ethyl 6-(2-cyanophenyl)-4-(3-fluorophenethylamino)nicotinate

Product 1

HCID 597449876-(2-cyanophenyl)-4-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamideYield 8.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of ethyl 6-(2-cyanophenyl)-4-(3-fluorophenethylamino)nicotinate (100 mg, 0.26 mmol) and 3-aminomethylpyridine (39 mg, 0.36 mmol) in toluene (1 mL) was added AlMe3 (0.2 mL, 2M in toluene, 0.39 mmol) at r.t. The reaction mixture was stirred at 70° C. overnight. The reaction was cooled, quenched with sat. NaHCO3, and diluted with EtOAc. The organic layer was separated, washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated under reduced pressure to give a crude oil. The crude mixture was purified on RP-HPLC using a mixture of acetonitrile and H2O to give 6-(2-cyanophenyl)-4-(3-fluorophenethylamino)-N-(pyridin-3-ylmethyl)nicotinamide (10 mg, 8.6%). LRMS (M+H+) m/z 452.0.

Workup

  1. temperatureThe reaction was cooled
  2. customquenched with sat. NaHCO3
  3. additiondiluted with EtOAc
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customto give a crude oil
  10. customThe crude mixture was purified on RP-HPLC
  11. additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record
ord-d73ff215eb6546039d20e2664de9cc89
Source dataset
uspto-grants-2011_04
Patent number
US07919511B2

Reaction notes

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