Nicotinic Acid → HCID 68982966, compound

HRID 1821879Notes

Reaction equation

HRID 1821879 reaction equation
[ClH:1].Cl.[NH:3]1[C:7]2=[CH:8][N:9]=[CH:10][CH:11]=[C:6]2[CH:5]=[C:4]1[CH2:12][NH2:13].[C:14](O)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[N:17][CH:16]=1.C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl.CN(C=O)C>[ClH:1].[ClH:1].[NH:3]1[C:7]2=[CH:8][N:9]=[CH:10][CH:11]=[C:6]2[CH:5]=[C:4]1[CH2:12][NH:13][C:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[N:17][CH:16]=1

Participants

8

Reactant 5

HCID 938Nicotinic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 689807071-(1H-Pyrrolo[2,3-c]pyridin-2-yl)methanamine--hydrogen chloride (1/2)

Product 1

HCID 68982966HCID 68982966, compoundYield 38.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (1H-pyrrolo[2,3-c]pyridin-2-yl)methylamine dihydrochloride (Example 84) (110 mg, 0.50 mmol), nicotinic acid (62 mg, 0.50 mmol), diisopropylethylamine (0.44 mL, 2.5 mmol), EDCI (110 mg, 0.55 mmol) and HOBt (cat.) in methylene chloride (2.9 mL) and DMF (3 mL) was stirred at room temperature under a nitrogen atmosphere overnight (18 h). The reaction mixture was concentrated to dryness under reduced pressure. The residue was diluted with water. The water layer was concentrated to dryness. The residue was dissolved in ethanol (10 mL) and 2 N HCl in Et2O (10 mL) was added. Methanol (ca. 5 mL) was added to dissolve the majority of material. The remaining brown precipitate was filtered off and discarded. The filtrate was concentrated, and the resulting solid was triturated with EtOH (ca. 4 mL), filtered, and dried to provide N-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)nicotinamide dihydrochloride (31 mg, 19%) as a tan solid: 1H NMR (500 MHz, CD3OD) δ4.99 (2H, s), 7.00 (1H, s), 8.03 (1H, d, J=6.0 Hz), 8.17-8.24 (3H, m), 8.77 (1H, s), 9.04-9.12 (3H, m), 9.38 (1H, s); ESI MS m/z 253 [C14H12N4O+H]+; HPLC (Method A) >99% (AUC), tR=7.78 min.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  2. additionThe residue was diluted with water
  3. concentrationThe water layer was concentrated to dryness
  4. dissolutionThe residue was dissolved in ethanol (10 mL)
  5. addition2 N HCl in Et2O (10 mL) was added
  6. additionMethanol (ca. 5 mL) was added
  7. dissolutionto dissolve the majority of material
  8. filtrationThe remaining brown precipitate was filtered off
  9. concentrationThe filtrate was concentrated
  10. customthe resulting solid was triturated with EtOH (ca. 4 mL)
  11. filtrationfiltered
  12. customdried

Sources & evidence

ORD record
ord-c917221a94784c6eaab6b41b23893c69
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

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