Diisopropylethylamine → HCID 178425492, compound

HRID 1623356Notes

Reaction equation

HRID 1623356 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]([OH:40])[CH2:36][CH2:35]1.CCN(C(C)C)C(C)C>CS(C)=O.O>[Cl:1][C:2]1[C:3]([C:25]2[C:30]([Cl:31])=[CH:29][N:28]=[C:27]([NH:33][C@H:34]3[CH2:39][CH2:38][C@H:37]([OH:40])[CH2:36][CH2:35]3)[CH:26]=2)=[N:4][C:5]([NH:8][CH2:16][CH:17]2[CH2:22][CH2:21][O:20][C:19]([CH3:23])([CH3:24])[CH2:18]2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 66936866HCID 66936866, compoundHCID 178511715HCID 178511715, compound

Product 1

HCID 178425492HCID 178425492, compoundYield 77.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
135 °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 (30 mg, 0.062 mmol) in DMSO (0.4 mL) was added trans-4-aminocyclohexanol (36 mg, 0.31 mmol) and DIEA (0.022 mL, 0.12 mmol). The mixture was stirred at 135° C. for 3 hr. The cooled reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were dried (Na2SO4), 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 crude resulting residue was purified by reverse phase HPLC and lyophilized to give 23 mg of trans-4-(3,5′-dichloro-6-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)amino-2,4′-bipyridin-2′-yl-amino)cyclohexanol as its TFA salt. LCMS (m/z): 479.3 (MH+), retention time=0.72 min; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.96 (d, J=12.91 Hz, 2H) 1.08 (s, 6H) 1.15-1.35 (m, 4H) 1.54 (d, J=12.91 Hz, 2H) 1.71-2.10 (m, 5H) 3.00 (d, J=6.65 Hz, 2H) 3.31-3.63 (m, 5H) 6.47 (s, 1H) 6.58 (d, 1H) 7.50 (d, J=9.00 Hz, 1H) 8.05 (s, 1H)

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe resulting residue was re-dissolved in trifluoroacetic acid (1 mL)
  7. stirringstirred for 15 min at ambient temperature
  8. concentrationconcentrated under reduced pressure
  9. customThe crude resulting residue
  10. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-62255cd2ecef44a894297b198b9fd6f8
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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