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

HRID 1921040Notes

Reaction equation

HRID 1921040 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

8

Reactant 6

HCID 111,2-DichloroethaneHCID 962WaterHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 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—0.40 H2O: C, 69.66; H, 6.40; N, 17.10. Found: C, 69.99; H, 6.27; N, 16.84.

Workup

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

Sources & evidence

ORD record
ord-c0093f5f288e401d85a8339fc86065fe
Source dataset
uspto-grants-2012_05
Patent number
US08173646B2

Reaction notes

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