Nicotinic Acid → Phenyl-(4-{4-[(pyridine-3-carbonyl)-amino]-phenyl}-piperazin-1-yl)-acetic acid methyl ester

HRID 1927614Notes

Reaction equation

HRID 1927614 reaction equation
[CH3:1][O:2][C:3](=[O:24])[CH:4]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=2)[CH2:13][CH2:12]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[C:25](O)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[N:28][CH:27]=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.O>[CH3:1][O:2][C:3](=[O:24])[CH:4]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)[N:11]1[CH2:12][CH2:13][N:14]([C:17]2[CH:18]=[CH:19][C:20]([NH:23][C:25]([C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)=[O:32])=[CH:21][CH:22]=2)[CH2:15][CH2:16]1

Participants

7

Reactant 4

HCID 938Nicotinic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69305249HCID 69305249, compound

Product 1

HCID 16665212Phenyl-(4-{4-[(pyridine-3-carbonyl)-amino]-phenyl}-piperazin-1-yl)-acetic acid methyl esterYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of [4-(4-amino-phenyl)-piperazin-1-yl]-phenyl-acetic acid methyl ester (50 mg, 0.15 mmol), nicotinic acid (23 mg, 0.18 mmol), and HATU (70 mg, 0.18 mmol) in DMF (2 mL) was treated with iPr2NEt (32 μL, 0.18 mmol). After 16 h, the mixture was diluted with H2O and extracted with DCM. The organic layer was washed with satd. aq. NaHCO3 and brine, dried (MgSO4), and concentrated to give an oil, which was purified by PTLC to give a tan solid (51 mg, 77%). MS (ESI): mass calcd. for C25H26N4O3, 430.50; m/z found, 431.4 [M+H]+. 1H NMR (CDCl3): 9.07-9.06 (m, 1H), 8.77-8.76 (m, 1H), 8.20-8.18 (m, 1H), 8.01 (s, 1H), 7.68 (br s, 1H), 7.51-7.42 (m, 4H), 7.38-7.32 (m, 3H), 6.92-6.90 (m, 2H), 4.06 (s, 1H), 3.71 (s, 3H), 3.22-3.20 (m, 4H), 2.64-2.62 (m, 4H).

Workup

  1. extractionextracted with DCM
  2. washThe organic layer was washed with satd
  3. dry with materialaq. NaHCO3 and brine, dried (MgSO4)
  4. concentrationconcentrated
  5. customto give an oil, which
  6. customwas purified by PTLC

Sources & evidence

ORD record
ord-bdcc361d72ac485a9f1aa2b0206316b0
Source dataset
uspto-grants-2012_05
Patent number
US08183239B2

Reaction notes

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