Dimethylformamide → HCID 11603483, compound

HRID 1446510Notes

Reaction equation

HRID 1446510 reaction equation
CN(C=O)C.[CH3:6][O:7][C:8]1[CH:9]=[C:10](/[CH:20]=[CH:21]/[C:22]([OH:24])=O)[CH:11]=[CH:12][C:13]=1[N:14]1[CH:18]=[C:17]([CH3:19])[N:16]=[CH:15]1.[O:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]([NH2:35])[CH2:27][CH2:26]1.C1C=CC2N(O)N=NC=2C=1>C(OCC)(=O)C.O.C(Cl)CCl>[O:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]([NH:35][C:22](=[O:24])/[CH:21]=[CH:20]/[C:10]2[CH:11]=[CH:12][C:13]([N:14]3[CH:18]=[C:17]([CH3:19])[N:16]=[CH:15]3)=[C:8]([O:7][CH3:6])[CH:9]=2)[CH2:27][CH2:26]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 49619573,4-Dihydro-2H-1-benzopyran-4-amineHCID 59528030(E)-3-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]acrylic acid

Product 1

HCID 11603483HCID 11603483, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a DMF (4 mL) solution of (E)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylic acid (70 mg) obtained in Example 121, chroman-4-ylamine (CAS#53981-38-7) (49 mg), EDC (62 mg) and HOBT (44 mg) were added at room temperature under nitrogen atmosphere, and the reaction solution was agitated at room temperature for 17 hours. Water and ethyl acetate were added to the reaction solution, and the organic layer was partitioned. The organic layer was washed with a saturated sodium chloride solution, and the organic layer was concentrated under reduced pressure after dried over anhydrous magnesium sulfate. The obtained residue was purified by silica gel chromatography (elution solvent:methanol-ethyl acetate system), and (E)-N-(chroman-4-yl)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]acrylamide racemate (90 mg) was obtained. This compound (50 mg) was separated by CHIRALPAK™ AD-H (2 cm×25 cm: mobile phase; hexane-ethanol 20%) available from Daicel Chemical Industries, Ltd., and the title optically-active substance with a retention time of 22 minutes (16 mg;>99% ee) and the title optically-active substance with a retention time of 28 minutes (19 mg;>98% ee) were obtained. The physical properties of the title optically-active substance with a retention time of 22 minutes (Example 413) are as follows.

Workup

  1. customthe organic layer was partitioned
  2. washThe organic layer was washed with a saturated sodium chloride solution
  3. concentrationthe organic layer was concentrated under reduced pressure
  4. dry with materialafter dried over anhydrous magnesium sulfate
  5. customThe obtained residue was purified by silica gel chromatography (elution solvent:methanol-ethyl acetate system)

Sources & evidence

ORD record
ord-4f3462e826b642669dd760ff4e47d85f
Source dataset
uspto-grants-2010_02
Patent number
US07667041B2

Reaction notes

Loading…