Diisopropylethylamine → Tert-butyl 4-(6-((3-fluoro-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)methylcarbamoyl)pyridin-3-yl)piperazine-1-carboxylate

HRID 711258Notes

Reaction equation

HRID 711258 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]([C:20](O)=[O:21])=[N:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:23][C:24]1[C:25]([C:32]2[CH:37]=[CH:36][N:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=2)=[N:26][CH:27]=[C:28]([CH2:30][NH2:31])[CH:29]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[F:23][C:24]1[C:25]([C:32]2[CH:37]=[CH:36][N:35]=[C:34]([C:38]([F:41])([F:39])[F:40])[CH:33]=2)=[N:26][CH:27]=[C:28]([CH2:30][NH:31][C:20]([C:17]2[N:18]=[CH:19][C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]3)=[CH:15][CH:16]=2)=[O:21])[CH:29]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67208645(3-Fluoro-2'-(trifluoromethyl)-[2,4'-bipyridin]-5-yl)methanamineHCID 729428105-(4-(tert-Butoxycarbonyl)piperazin-1-yl)picolinic acid

Product 1

HCID 68079197Tert-butyl 4-(6-((3-fluoro-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)methylcarbamoyl)pyridin-3-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 5-(4-(tert-butoxycarbonyl)piperazin-1-yl)picolinic acid 49-4 (92 mg, 0.3 mmol), (3-fluoro-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methanamine 84-2 (81 mg, 0.3 mmol) and HATU (114 mg, 0.3 mmol) in DMF (1.5 mL) was added DIEA (0.15 mL, 0.9 mmol). The mixture was stirred at room temperature for 2 hours. The mixture was diluted with ethyl acetate (100 mL), washed with H2O and brine, dried over Na2SO4, and concentrated to dryness by rotary evaporation. The crude product was purified by silica gel flash chromatography, and eluted with 5% methanol in dichloromethane to give tert-butyl 4-(6-((3-fluoro-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methylcarbamoyl)pyridin-3-yl)piperazine-1-carboxylate 49-5 as a pale yellow oil. MS m/z 561.2 (M+1)

Workup

  1. washwashed with H2O and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated to dryness by rotary evaporation
  4. customThe crude product was purified by silica gel flash chromatography
  5. washeluted with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-e0e9058fc269408594d9e1895b21f5a9
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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