Nicotinic Acid → HCID 57893530, compound

HRID 1821847Notes

Reaction equation

HRID 1821847 reaction equation
Cl.Cl.[C:3]1([CH:9]([NH2:19])[C:10]2[NH:18][C:13]3=[CH:14][N:15]=[CH:16][CH:17]=[C:12]3[CH:11]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.[C:29](O)(=[O:36])[C:30]1[CH:35]=[CH:34][CH:33]=[N:32][CH:31]=1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:3]1([CH:9]([C:10]2[NH:18][C:13]3=[CH:14][N:15]=[CH:16][CH:17]=[C:12]3[CH:11]=2)[NH:19][C:29](=[O:36])[C:30]2[CH:35]=[CH:34][CH:33]=[N:32][CH:31]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 938Nicotinic AcidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68982590HCID 68982590, compound

Product 1

HCID 57893530HCID 57893530, compoundYield 32.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-phenyl-1-(1H-pyrrolo[2,3-c]pyridin-2-yl)methylamine dihydrochloride (Example 40) (51 mg, 0.17 mmol), N,N-diisopropylethylamine (DIPEA) (0.15 mL, 0.85 mmol) and nicotinic acid (22 mg, 0.18=mmol) in methylene chloride (2.0 mL) was added 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride (EDC-HCl) (30 mg, 0.20 mmol) followed by a catalytic amount of 4-dimethylaminopyridine (DMAP). The reaction mixture was stirred at room temperature overnight (20 h) under a N2 atmosphere. TLC analysis showed the starting amine, therefore the reaction mixture was heated to reflux. After refluxing overnight, the reaction mixture was concentrated to dryness. The residue was dissolved in EtOAc and water. The organic layer was washed with water, 1 M citric acid, saturated NaHCO3, and saturated NaCl. TLC analysis showed that the majority of desired product was extracted into the 1 M citric acid washing. The citric acid extracts were made basic with 15% NaOH solution and extracted with methylene chloride. The organic extracts were dried over Na2SO4, filtered and concentrated to dryness. Trituration with Et2O/CH2Cl2 (1:1) provided N-[phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methyl]nicotinamide (18 mg, 32%) as a light yellow solid after drying: mp 178-188° C.; 1H NMR (300 MHz, CD3OD) δ6.30 (1H, s), 6.67 (1H, s), 7.35-7.55 (7H, m), 8.03 (1H, d, J=5.5 Hz), 8.30-8.38 (1H, m), 8.61 (1H, s), 8.69-8.71 (1H, m), 9.05-9.07 (1H, m); ESI MS m/z 329 [C20H16N4O+H]+; HPLC (Method A) >99% (AUC) tR=13.3 min.

Workup

  1. temperaturethe reaction mixture was heated to reflux
  2. temperatureAfter refluxing overnight
  3. concentrationthe reaction mixture was concentrated to dryness
  4. dissolutionThe residue was dissolved in EtOAc
  5. washThe organic layer was washed with water, 1 M citric acid, saturated NaHCO3, and saturated NaCl
  6. extractionwas extracted into the 1 M citric acid washing
  7. extractionextracted with methylene chloride
  8. dry with materialThe organic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-e0fe6f36586041f99feb155ef0af3b1b
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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