Diisopropylethylamine → HCID 178425495, compound

HRID 1623357Notes

Reaction equation

HRID 1623357 reaction equation
[Cl:1][C:2]1[C:3]([C:25]2[C:30]([Cl:31])=[CH:29][N:28]=[C:27](F)[CH:26]=2)=[N:4][C:5]([N:8]([CH2:16][CH:17]2[CH2:22][CH2:21][O:20][C:19]([CH3:24])([CH3:23])[CH2:18]2)C(=O)OC(C)(C)C)=[CH:6][CH:7]=1.[NH2:33][C@H:34]1[CH2:39][CH2:38][C@H:37](N)[CH2:36][CH2:35]1.CC[N:43](C(C)C)C(C)C>CS(C)=O.O>[NH2:33][C@H:34]1[CH2:39][CH2:38][C@H:37]([C:7]2[CH:6]=[C:5]([NH:8][CH2:16][CH:17]3[CH2:22][CH2:21][O:20][C:19]([CH3:23])([CH3:24])[CH2:18]3)[N:4]=[C:3]([C:25]3[C:30]([Cl:31])=[CH:29][N:28]=[C:27]([NH2:43])[CH:26]=3)[C:2]=2[Cl:1])[CH2:36][CH2:35]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 66936866HCID 66936866, compoundHCID 178511674HCID 178511674, compound

Product 1

HCID 178425495HCID 178425495, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of tert-butyl 3,5′-dichloro-2′-fluoro-2,4′-bipyridin-6-yl((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)carbamate (40 mg, 0.083 mmol) in DMSO (0.4 mL) was added trans-1,4-diaminocyclohexane (47 mg, 0.41 mmol) and DIEA (0.029 mL, 0.17 mmol). The mixture was stirred at 120° C. for 2 hr. The cooled reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed sequentially with water and brine, dried over sodium sulfate, filtered, and concentrated. The resulting residue was re-dissolved in trifluoroacetic acid (1 mL), stirred for 15 min at ambient temperature, and then concentrated under reduced pressure. The resulting residue was taken up in DCM, washed with saturated aqueous sodium bicarbonate, dried (Na2SO4), filtered, and concentrated to give 39 mg of NT-(trans-4-aminocyclohexyl)-3,5′-dichloro-N6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridine-2′,6-diamine. LCMS (m/z): 478.4 (MH+), retention time=0.64 min.

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed sequentially with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe resulting residue was re-dissolved in trifluoroacetic acid (1 mL)
  8. stirringstirred for 15 min at ambient temperature
  9. concentrationconcentrated under reduced pressure
  10. washwashed with saturated aqueous sodium bicarbonate
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-013bfb1f91a54d73b395584411a20b41
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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