Diisopropylethylamine → 5-Formyl-4'-methyl-N-((6-methylpyridin-3-yl)methyl)biphenyl-3-carboxamide

HRID 1845340Notes

Reaction equation

HRID 1845340 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([C:16]([OH:18])=O)[CH:6]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=2)[CH:8]=1)=[O:2].[CH3:19][C:20]1[N:25]=[CH:24][C:23]([CH2:26][NH2:27])=[CH:22][CH:21]=1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH:1]([C:3]1[CH:4]=[C:5]([C:16]([NH:27][CH2:26][C:23]2[CH:24]=[N:25][C:20]([CH3:19])=[CH:21][CH:22]=2)=[O:18])[CH:6]=[C:7]([C:9]2[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][CH:14]=2)[CH:8]=1)=[O:2]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12214337(6-Methylpyridin-3-yl)methanamineHCID 581880045-Formyl-4'-methylbiphenyl-3-carboxylic acid

Product 1

HCID 581882015-Formyl-4'-methyl-N-((6-methylpyridin-3-yl)methyl)biphenyl-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Into a round bottom flask were combined 5-formyl-4′-methylbiphenyl-3-carboxylic acid (3.00 g, 12.5 mmol), (6-methylpyridin-3-yl)methanamine (1.91 g, 15.6 mmol), N,N-diisopropylethylamine (6.46 g, 49.9 mmol) and N,N-dimethylformamide (97 mL). N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (9.50 g, 25.0 mmol) was added in one portion and the mixture was heated at 60° C. for 2 h. After cooling, the mixture was poured onto saturated sodium bicarbonate (200 mL) and extracted with ethyl acetate (3×100 mL). The combined extracts were dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography using methylene chloride:methanol gradient (0-10%) to afford the title compound. LC-MS: 346.2 [M+1]+; 1H NMR (400 MHz, DMSO-d6): 10.14 (s, 1H), 8.46-8.43 (m, 2H), 8.37-8.33 (m, 2H), 7.72 (d, 2H, J=8.0 Hz), 7.64 (dd, 1H, J=8.0 Hz), 7.34 (d, 2H, J=7.9 Hz), 7.22 (d, 2H, J=7.9 Hz), 4.51 (d, 2H, J=5.9 Hz), 2.44 (s, 3H), 2.37 (s, 3H).

Workup

  1. customInto a round bottom flask were combined
  2. temperatureAfter cooling
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-ebbb576e4bb74b04b1231e12e5382825
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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