Potassium Hydroxide → HCID 178493782, compound

HRID 1623400Notes

Reaction equation

HRID 1623400 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[N:9]=2)[C:5]([O:23][CH3:24])=[CH:4][N:3]=1.[C@H:25]1([NH2:32])[CH2:30][CH2:29][C@H:28]([NH2:31])[CH2:27][CH2:26]1.[OH-].[K+]>O1CCOCC1>[NH2:31][C@H:28]1[CH2:29][CH2:30][C@H:25]([NH:32][C:2]2[CH:7]=[C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][CH2:15][C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=4)[N:9]=3)[C:5]([O:23][CH3:24])=[CH:4][N:3]=2)[CH2:26][CH2:27]1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 86650643HCID 86650643, compoundHCID 178511674HCID 178511674, compound

Product 1

HCID 178493782HCID 178493782, compoundYield 17.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a scintillation vial was added 2′-chloro-N-(3-fluorobenzyl)-5′-methoxy-2,4′-bipyridin-6-amine (30 mg, 0.087 mmol), trans-cyclohexane-1,4-diamine (45 mg, 0.394 mmol), 1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidene(1,4-naphthoquinone)palladium(0) (11.4 mg, 8.73 μmol), KOH (45 mg, 0.802 mmol) and Dioxane (0.3 mL). The resulting mixture was stirred at 100° C. for 18 h. The mixture was concentrated in vacuo and then diluted with water. The resultant solid was filtered and washed with water (×3). The solid was then purified by reverse phase preparative HPLC and then lyophallized to yield N2′-(trans-4-aminocyclohexyl)-N6-(3-fluorobenzyl)-5′-methoxy-2,4′-bipyridine-2′,6-diamine (6.5 mg), LCMS (m/z): 422.3 (MH+), retention time=0.54 min as a TFA salt. 1H-NMR (400 MHz, METHANOL-d4, 25° C.) 1.40-1.66 (m, 4H) 2.05-2.25 (m, 4H) 3.10-3.25 (m, 1H) 3.55-3.64 (m, 1H) 3.86 (s, 3H) 4.57 (s, 2H) 6.69 (d, J=8.4 Hz, 1H) 6.92-7.00 (m, 1H) 7.10 (d, J=10.0 Hz, 1H) 7.17 (d, J=7.6 Hz, 1H) 7.28-7.33 (m, 2H) 7.48-7.52 (m, 2H) 7.53-7.58 (m, 1H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additiondiluted with water
  3. filtrationThe resultant solid was filtered
  4. washwashed with water (×3)
  5. customThe solid was then purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-1abd4aae140e42c4a7cede1c8c67baa9
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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