Dimethyl Sulfoxide → HCID 178510200, compound

HRID 1623305Notes

Reaction equation

HRID 1623305 reaction equation
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[C:13]([C:15]#[N:16])[CH:12]=[C:11]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.CS(C)=O.[C@H:30]1([NH2:37])[CH2:35][CH2:34][C@H:33]([NH2:36])[CH2:32][CH2:31]1>CCOC(C)=O>[NH2:36][C@H:33]1[CH2:34][CH2:35][C@H:30]([NH:37][C:5]2[CH:4]=[C:3]([C:9]3[CH:14]=[C:13]([C:15]#[N:16])[CH:12]=[C:11]([NH:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([F:25])[CH:20]=4)[N:10]=3)[C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:31][CH2:32]1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 669369675'-Chloro-2'-fluoro-6-(3-fluorobenzylamino)-2,4'-bipyridine-4-carbonitrileHCID 178511674HCID 178511674, compound

Product 1

HCID 178510200HCID 178510200, compoundYield 80.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

To a scintillation vial containing 5′-chloro-2′-fluoro-6-(3-fluorobenzylamino)-2,4′-bipyridine-4-carbonitrile (72 mg, 0.202 mmol) was added DMSO (3 ml) and trans-cyclohexane-1,4-diamine (230 mg, 2.018 mmol). The homogenous yellow reaction mixture was capped and heated to 105° C. in a oil bath for 3 hr. The reaction mixture was diluted with EtOAc and washed with sat NaHCO3, sat NaCl. The organic layer was dried Na2SO4, filtered and concentrated. The crude solid was purified by Prep HPLC and the collected fractions were combined and diluted with EtOAc and neutralized with sat NaHCO3 and then sat NaCl. The organic layer was dried over Na2SO4, filtered and concentrated to afford 2′-(trans-4-aminocyclohexylamino)-5′-chloro-6-(3-fluorobenzylamino)-2,4′-bipyridine-4-carbonitrile (73 mg, 80%). LCMS (m/z): 451.2 (MH+), retention time=0.70 min. 1H NMR (400 MHz, METHANOL-d4) d ppm 1.34-1.48 (m, 2H) 1.50-1.64 (m, 2H) 2.06-2.22 (m, 4H) 3.08-3.20 (m, 1H) 3.63-3.74 (m, 1H) 4.61 (s, 2H) 6.81 (s, 1H) 6.87 (s, 1H) 6.91-6.99 (m, 1H) 7.02 (s, 1H) 7.04-7.10 (m, 1H) 7.12-7.18 (m, 1H) 7.25-7.36 (m, 1H) 8.00 (s, 1H).

Workup

  1. customThe homogenous yellow reaction mixture was capped
  2. washwashed
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude solid was purified by Prep HPLC
  6. additiondiluted with EtOAc and neutralized with sat NaHCO3
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-394708aae3084d7e9844b24a7c6f9ac2
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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