Hydrochloric Acid → (E)-3-(2-{3-[2-(Phenylmethoxy)phenyl]phenyl}phenyl)-N-(2-thienylsulfonyl)prop-2-enamide

HRID 1168904Notes

Reaction equation

HRID 1168904 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]2[CH:16]=[C:17]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3/[CH:27]=[CH:28]/[C:29](O)=[O:30])[CH:18]=[CH:19][CH:20]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S:32]1[CH:36]=[CH:35][CH:34]=[C:33]1[S:37]([NH-:40])(=[O:39])=[O:38].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl.CC(O)=O>[C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]2[CH:16]=[C:17]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3/[CH:27]=[CH:28]/[C:29]([NH:40][S:37]([C:33]3[S:32][CH:36]=[CH:35][CH:34]=3)(=[O:39])=[O:38])=[O:30])[CH:18]=[CH:19][CH:20]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 12112238(E)-3-(2-{3-[2-(Phenylmethoxy)phenyl]phenyl}phenyl)prop-2-enoic acidHCID 865853752-Thiophenesulfonylamide

Product 1

HCID 10209488(E)-3-(2-{3-[2-(Phenylmethoxy)phenyl]phenyl}phenyl)-N-(2-thienylsulfonyl)prop-2-enamideYield 56.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To (E)-3-(2-{3-[2-(Phenylmethoxy)phenyl]phenyl}phenyl)prop-2-enoic acid (210 mg, 0.52 mmol) of Example 2 (step 2), 2-thiophenesulfonylamide (121 mg, 0.74 mmol) and DMAP (250 mg, 2.04 mmol) in CH2Cl2 (3 mL) was added EDCI (142 mg, 0.74 mmol). After stirring at r.t. for 2 days, the reaction mixture was poured into 1N HCl (or aqueous AcOH) and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. Purification by flash chromatography (Tol:EtOAc:AcOH, 1:0:0 to 20:1:0.1) and recrystallization (Hex:CH2Cl2) provided the desired material as a white solid (161 mg, 56%). 1H NMR (acetone-d6) δ 5.13 (2H, s), 6.72 (1H, d), 7.04 (1H, td), 7.1-7.2 (2H, m), 7.2-7.4 (8H, m), 7.4-7.5 (4H, m), 7.55 (1H, t), 7.62 (1H, dt), 7.7-7.8 (3H, m) and 7.92 (1H, dd).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification
  7. customby flash chromatography (Tol:EtOAc:AcOH, 1:0:0 to 20:1:0.1) and recrystallization (Hex:CH2Cl2)

Sources & evidence

ORD record
ord-29e2a94aa6e743d5b89d9cacfdee233d
Source dataset
uspto-grants-2003_09
Patent number
US06627656B2

Reaction notes

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