Trifluoroacetic acid → HCID 178478286, compound

HRID 1623404Notes

Reaction equation

HRID 1623404 reaction equation
[Cl:1][C:2]1[C:3]([C:16]2[C:21]([Cl:22])=[CH:20][N:19]=[C:18](F)[CH:17]=2)=[N:4][C:5]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:6][CH:7]=1.[NH2:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([N:31]([CH:39]2[CH2:43][CH2:42][O:41][CH2:40]2)C(=O)OC(C)(C)C)[CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.C(O)(C(F)(F)F)=O>CCOC(C)=O.CN1C(=O)CCC1>[Cl:1][C:2]1[C:3]([C:16]2[C:21]([Cl:22])=[CH:20][N:19]=[C:18]([NH:24][C@H:25]3[CH2:26][CH2:27][C@H:28]([NH:31][CH:39]4[CH2:43][CH2:42][O:41][CH2:40]4)[CH2:29][CH2:30]3)[CH:17]=2)=[N:4][C:5]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 581271593,5'-dichloro-2'-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4'-bipyridin-6-amineHCID 178452892HCID 178452892, compound

Product 1

HCID 178478286HCID 178478286, compoundYield 29.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

To a scintillation vial was added 3,5′-dichloro-2′-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridin-6-amine (25 mg, 0.070 mmol), racemic tert-butyl trans-4-aminocyclohexyl(tetrahydrofuran-3-yl)carbamate (21.95 mg, 0.077 mmol), DIPEA (24.51 μl, 0.140 mmol) and NMP (0.2 ml). This was heated at 110° C. for 48 h. The mixture was diluted with EtOAc and washed with water (×2), saturated brine (×2), then dried (Na2SO4), filtered and evaporated under reduced pressure. The resulting residue was dissolved in CH2Cl2 (0.4 mL) and treated with TFA (100 μl, 1.298 mmol). After 30 minutes, the mixture was concentrated in vacuo and the resulting residue was purified by reverse phase preparative HPLC and then lyophallized to yield racemic 3,5′-dichloro-N6-((tetrahydro-2H-pyran-4-yl)methyl)-N2′-(trans-4-(tetrahydrofuran-3-yl-amino)cyclohexyl)-2,4′-bipyridine-2′,6-diamine (10.8 mg), LCMS (m/z): 520.1/522.0 (bis-chloro isotopic signature for MH+), retention time=0.59 min as a TFA salt.

Workup

  1. washwashed with water (×2), saturated brine (×2)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated under reduced pressure
  5. dissolutionThe resulting residue was dissolved in CH2Cl2 (0.4 mL)
  6. concentrationthe mixture was concentrated in vacuo
  7. customthe resulting residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-89fc3ac660ac499891b92b90c15c5202
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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