Potassium trimethylsilanolate → 5-{[(1R,2S)-2-aminocyclohexyl]amino}-3-[(6-ethylpyridin-2-yl)amino]pyridine-2-carboxamide

HRID 1504879Notes

Reaction equation

HRID 1504879 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[CH:10]=[C:11]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][CH3:25])[N:19]=2)[C:12]([C:15]#[N:16])=[N:13][CH:14]=1.C[Si](C)(C)[O-:28].[K+]>O1CCOCC1>[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[CH:10]=[C:11]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][CH3:25])[N:19]=2)[C:12]([C:15]([NH2:16])=[O:28])=[N:13][CH:14]=1

Participants

4

Reactant 2

HCID 23668039Potassium trimethylsilanolateHCID 867317505-{[(1R,2S)-2-amino cyclohexyl]amino}-3-[(6-ethylpyridin-2-yl)amino]pyridine-2-carbonitrile

Product 1

HCID 715474215-{[(1R,2S)-2-aminocyclohexyl]amino}-3-[(6-ethylpyridin-2-yl)amino]pyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 5-{[(1R,2S)-2-aminocyclohexyl]amino}-3-[(6-ethylpyridin-2-yl)amino]pyridine-2-carbonitrile (51 mg, 0.152 mmol) and potassium trimethylsilanolate (486 mg, 3.79 mmol) in dioxane (3 mL) was heated to 100° C. for 3 hours. The reaction mixture was allowed to cool to room temperature, filtered, and concentrated under reduced pressure. The residue was dissolved in DMSO, filtered, and purified via reverse phase HPLC (acetonitrile/water with 0.1% TFA, linear gradient) to afford 5-{[(1R,2S)-2-aminocyclohexyl]amino}-3-[(6-ethylpyridin-2-yl)amino]pyridine-2-carboxamide. MS ESI calc'd. for C19H27N6O[M+H]+ 355. found 355. 1H NMR (500 MHz, DMSO-d6) δ 11.84 (s, 1H), 8.56 (s, 1H), 7.92 (s, 1H), 7.88-7.80 (m, 2H), 7.70 (d, J=2.5 Hz, 1H), 7.58-7.54 (m, 1H), 7.34 (s, 1H), 6.76 (d, J=7.3 Hz, 1H), 6.65 (d, J=8.2 Hz, 1H), 6.34 (d, J=8.4 Hz, 1H), 3.81 (br s, 1H), 2.68 (q, J=7.5 Hz, 2H), 1.86-1.79 (m, 2H), 1.73-1.67 (m, 1H), 1.67-1.54 (m, 3H), 1.45-1.35 (m, 2H), 1.24 (t, J=7.6 Hz, 3H).

Workup

  1. temperatureto cool to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in DMSO
  5. filtrationfiltered
  6. custompurified via reverse phase HPLC (acetonitrile/water with 0.1% TFA, linear gradient)

Sources & evidence

ORD record
ord-18cac594326b4ee9a6f032fe2690c5ae
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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