1,2-Dichloroethane → 3-(6-Aminopyridin-3-Yl)-N-Methyl-N-((1-Methyl-1h-Indol-2-Yl)Methyl)Acrylamide

HRID 2112693Notes

Reaction equation

HRID 2112693 reaction equation
C(Cl)CCl.[NH2:5][C:6]1[N:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]([OH:16])=O)=[CH:8][CH:7]=1.[CH3:17][N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[C:19]1[CH2:27][NH:28][CH3:29].C1C=CC2N(O)N=NC=2C=1.O.C(N(CC)CC)C>CN(C=O)C>[NH2:5][C:6]1[N:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]([N:28]([CH3:29])[CH2:27][C:19]2[N:18]([CH3:17])[C:26]3[C:21]([CH:20]=2)=[CH:22][CH:23]=[CH:24][CH:25]=3)=[O:16])=[CH:8][CH:7]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 10487224(2E)-3-(6-aminopyridin-3-yl)prop-2-enoic acidHCID 11401058methyl((1-methyl-1H-indol-2-yl)methyl)amine

Product 1

HCID 52877203-(6-Aminopyridin-3-Yl)-N-Methyl-N-((1-Methyl-1h-Indol-2-Yl)Methyl)AcrylamideYield 84.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (0.70 g, 3.7 mmole) was added to a solution of (E)-3-(6-aminopyridin-3-yl)acrylic acid (0.61 g, 3.7 mmole), 1-methyl-2-(methylaminomethyl)-1H-indole (0.65 g, 3.7 mmole), HOBt H2O (0.50 g, 3.7 mmole), and triethylamine (0.52 mL, 3.7 mmole) in DMF (30 mL) at RT. The reaction was stirred overnight, then was concentrated in vacuo. The residue was diluted with 5% NaHCO3 and extracted with CH2Cl2. The combined organic extracts were washed with brine and dried over MgSO4—Flash chromatography on silica gel (3% MeOH/CH2Cl2) gave a colorless semisolid which was triturated with Et2O and dried. The title compound (1.0 g, 83%) was obtained as a white solid: 1H NMR (300 MHz, CDCl3) δ 8.20 (br s, 1H), 7.45-7.70 (m, 3H), 7.00-7.30 (m, 3H), 6.69 (d, J=15.4 Hz, 1H), 6.30-6.50 (m, 2H), 4.89 (s, 2H), 4.67 (br s, 2H), 3.68 (s, 3H), 3.01 (s, 3H); MS (ES) m/e 321 (M+H)+. Anal. Calcd for C19H20N4O.0.40H2O: C, 69-66; H, 6.40; N, 17.10. Found: C, 69.99; H, 6.27; N, 16.84.

Workup

  1. concentrationwas concentrated in vacuo
  2. additionThe residue was diluted with 5% NaHCO3
  3. extractionextracted with CH2Cl2
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4—Flash chromatography on silica gel (3% MeOH/CH2Cl2)
  6. customgave a colorless semisolid which
  7. customwas triturated with Et2O
  8. customdried

Sources & evidence

ORD record
ord-629e7b635f35491c8be326fa033ff73f
Source dataset
uspto-grants-2009_04
Patent number
US07524843B2

Reaction notes

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