1,2-Dichloroethane → (E)-3-(6-Aminopyridin-3-yl)-N-methyl-N-(1-methyl-1H-indazol-3-ylmethyl)acrylamide

HRID 1921042Notes

Reaction equation

HRID 1921042 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)[C:20]([CH2:27][NH:28][CH3:29])=[N:19]1.C1C=CC2N(O)N=NC=2C=1.O.CCN(CC)CC>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:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:18]([CH3:17])[N:19]=2)=[O:16])=[CH:8][CH:7]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 962WaterHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 7537473N-Methyl-N-[(1-methyl-1H-indazol-3-yl)methyl]amineHCID 10487224(2E)-3-(6-aminopyridin-3-yl)prop-2-enoic acid

Product 1

HCID 9797187(E)-3-(6-Aminopyridin-3-yl)-N-methyl-N-(1-methyl-1H-indazol-3-ylmethyl)acrylamideYield 74.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

EDC (230 mg, 1.2 mmole) was added to a solution (E)-3-(6-aminopyridin-3-yl)acrylic acid (164 mg, 1.0 mmole), 1-methyl-3-(methylaminomethyl)-1H-indazole (210 mg, 1.2 mmole), HOBt.H2O (162 mg, 1.2 mmole), and Et3N (0.28 mL, 2.0 mmole) in dry DMF (5 mL) at RT. After 18 hr the mixture was concentrated. Flash chromatography on silica gel (5% EtOH/EtOAc) gave the title compound (238 mg, 74%) as a white foam: 1H NMR (400 MHz, CDCl3) δ 8.24 (m, 1H), 7.90 (m, 1H), 7.65 (m, 2H), 7.35 (m, 2H), 7.09 (m, 1H), 6.73 (m, 1H), 6.50 (m, 1H), 5.04 (s, 2H), 4.83 (bs, 2H), 4.04 (s, 3H), 3.10 (s, 3H); MS (ES) m/e 322 (M+H)+.

Workup

  1. customat RT
  2. concentrationAfter 18 hr the mixture was concentrated

Sources & evidence

ORD record
ord-512ea275344e4b158b5aad442d7aa749
Source dataset
uspto-grants-2012_05
Patent number
US08173646B2

Reaction notes

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