Diisopropylethylamine → HCID 68727626, compound

HRID 2093616Notes

Reaction equation

HRID 2093616 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][N:6]=1)=[O:4].[F:14][C:15]([F:31])([F:30])[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([N:22]2[CH2:27][CH2:26][CH:25]([CH2:28][NH2:29])[CH2:24][CH2:23]2)[N:17]=1.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH:29][CH2:28][CH:25]2[CH2:26][CH2:27][N:22]([C:18]3[N:17]=[C:16]([C:15]([F:31])([F:30])[F:14])[CH:21]=[CH:20][N:19]=3)[CH2:23][CH2:24]2)=[O:11])=[CH:7][N:6]=1)=[O:4]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 5796316-(Methoxycarbonyl)pyridine-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59586070HCID 59586070, compound2×HCID 178418300HCID 178418300, compound

Product 1

HCID 68727626HCID 68727626, compoundYield 46.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(methoxycarbonyl)nicotinic acid (250 mg, 1.39 mmol) and 1-{1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methanamine (INTERMEDIATE 6, 361 mg, 1.39 mmol) in dimethylformamide (5.0 ml) were added hydroxybenzotriazole (225 mg, 1.67 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (320 mg, 1.67 mmol), and N,N-diisopropylethylamine (291 μl, 1.67 mmol). The reaction was allowed to stir at ambient temperature for 18 h. After removal of the solvent by evaporation, the residue was purified by flash chromatography on a silica gel column, eluting with a gradient of 0-100% ethyl acetate in hexanes to give the title compound as a white solid (272.2 mg). Mass spectrum (ESI) 425 (M+1). 1H NMR (500 MHz, CDCl3) δ 9.13 (s, 1H), 8.49 (d, 1H, J=4.8 Hz), 8.33 (d, 1H, J=8.0 Hz), 8.24 (d, 1H, J=8 Hz), 6.73-6.77 (m, 2H), 4.87 (d, 2H, J=13.5 Hz), 4.05 (s, 3H), 3.44-3.47 (m, 2H), 2.90-2.98 (m, 2H), 1.90-2.00 (m, 1H), 1.90 (d, 2H, J=12.6 Hz), 1.27-1.36 (m, 2H).

Workup

  1. customAfter removal of the solvent
  2. customby evaporation
  3. customthe residue was purified by flash chromatography on a silica gel column
  4. washeluting with a gradient of 0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4616ca2195ec405da2a99a656920f084
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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