1,2-Dichloroethane → (E)-3-(6-Amino-pyridin-3-yl)-N-(2-ethoxy-3-methoxy-benzyl)-N-methyl-acrylamide hydrochloride

HRID 1362241Notes

Reaction equation

HRID 1362241 reaction equation
C(Cl)C[Cl:3].[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.[CH2:17]([O:19][C:20]1[C:28]([O:29][CH3:30])=[CH:27][CH:26]=[CH:25][C:21]=1[CH2:22]CN)[CH3:18].C1C=CC2N(O)N=[N:37][C:35]=2C=1.O.CCN(C(C)C)C(C)C.Cl>CN(C=O)C.O.C(Cl)Cl>[ClH:3].[NH2:5][C:6]1[N:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]([N:37]([CH2:22][C:21]2[CH:25]=[CH:26][CH:27]=[C:28]([O:29][CH3:30])[C:20]=2[O:19][CH2:17][CH3:18])[CH3:35])=[O:16])=[CH:8][CH:7]=1

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 47154242-(2-Ethoxy-3-methoxyphenyl)ethanamineHCID 10487224(2E)-3-(6-aminopyridin-3-yl)prop-2-enoic acid

Product 1

HCID 66966862(E)-3-(6-Amino-pyridin-3-yl)-N-(2-ethoxy-3-methoxy-benzyl)-N-methyl-acrylamide hydrochlorideYield 46%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

EDC (231 mg, 1.2 mmol) was added to a solution of (E)-3-(6-amino-pyridin-3-yl)acrylic acid (164 mg, 1.0 mmol), (2-ethoxy-3-methoxy-benzyl)methylamine (215 mg, 1.1 mmol), HOBt H2O (149 mg, 1.1 mmol) and DIPEA (525 μL, 3.0 mmol) in dry DMF (10 mL). After 18 hr of stirring, the mixture was diluted with water (60 mL) and extracted with EtOAc (2×20 mL). The organic layer was washed with brine (2×30 mL), dried and evaporated. Flash chromatography (silica 1-3% MeOH in CH2Cl2) furnished pure free base which was dissolved in CH2Cl2 (10 mL). After addition of HCl (1.5 mL, 1M in ether), the solvents were evaporated and the residue was washed with ether and dried to afford the title compound (172 mg, 46%). 1H NMR (300 MHz, DMSO-d6) δ 8.28 (m, 3H), 7.48 and 7.45 (rotamers, 2d, J=15.4 Hz, 1H), 7.25 and 7.23 (rotamers, 2d, J=15.4 Hz, 1H), 7.00 (m, 3H), 6.62 (m, 1H), 4.78 and 4.63 (rotamers, 2s, 2H), 3.98 (m, 2H), 3.79 (s, 3H), 3.08 and 2.84 (rotamers, 2s, 3H), 1.28 (m, 3H). MS (ESI) m/e 342 (M+H)+.

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. washThe organic layer was washed with brine (2×30 mL)
  3. customdried
  4. customevaporated
  5. customFlash chromatography (silica 1-3% MeOH in CH2Cl2) furnished pure free base which
  6. customthe solvents were evaporated
  7. washthe residue was washed with ether
  8. customdried

Sources & evidence

ORD record
ord-70d053e4bd1045eb8e546d0b3115fd75
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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