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

HRID 1711923Notes

Reaction equation

HRID 1711923 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.[CH:17]([O:20][C:21]1[C:29]([O:30][CH3:31])=[CH:28][CH:27]=[CH:26][C:22]=1[CH2:23]CN)([CH3:19])[CH3:18].C1C=CC2N(O)N=[N:38][C:36]=2C=1.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:38]([CH2:23][C:22]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH3:31])[C:21]=2[O:20][CH:17]([CH3:18])[CH3:19])[CH3:36])=[O:16])=[CH:8][CH:7]=1

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10487224(2E)-3-(6-aminopyridin-3-yl)prop-2-enoic acidHCID 12176049(2-Isopropoxy-3-methoxy-benzyl)methylamine

Product 1

HCID 66967294(E)-3-(6-amino-pyridin-3-yl)-N-(2-isopropoxy-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-isopropoxy-3-methoxy-benzyl)methylamine (230 mg, 1.1 mmol), HOBt*H2O (149 mg, 1.1 mmol) and DIPEA (525 μL, 3.0 mmol) in dry DMF (10. L). 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) of the residue 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; the residue was washed with ether and dried to afford the title compound (180 mg, 46%). 1H NMR (300 MHz, DMSO-d6) 67 8.31 (m, 3H), 7.46 and 7.45 (rotamers, 2d, J=15.4 Hz, 1H), 7.23 and 7.17 (rotamers, 2d, J=15.4 Hz, 1H), 6.99 (m, 3H), 6.62 (m, 1H), 4.76 and 4.63 (rotamers, 2s, 2H), 4.51 (m, 1H), 3.79 (s, 3H), 3.06 and 2.85 (rotamers, 2s, 3H), 1.22 (d, J=6.1 Hz, 3H) 1.21 (d, J=6.1 Hz, 3H). MS (ESI) m/e 356 (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) of the residue furnished pure free base which
  6. customwere evaporated
  7. washthe residue was washed with ether
  8. customdried

Sources & evidence

ORD record
ord-4abd4d78330547e69fa8d97b3036e2cd
Source dataset
uspto-grants-2010_09
Patent number
US07790709B2

Reaction notes

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