1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 53361692, compound

HRID 1023377Notes

Reaction equation

HRID 1023377 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:24]=[CH:25]/[C:26]([OH:28])=O)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[CH:11][N:10]=1.[CH3:29][O:30][C:31]1[CH:32]=[C:33]([CH:50]=[CH:51][CH:52]=1)[O:34][CH2:35][CH2:36][C:37]1[CH:49]=[CH:48][C:40]([CH2:41][N:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)=[CH:39][CH:38]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4](/[CH:24]=[CH:25]/[C:26]([N:45]2[CH2:44][CH2:43][N:42]([CH2:41][C:40]3[CH:48]=[CH:49][C:37]([CH2:36][CH2:35][O:34][C:33]4[CH:50]=[CH:51][CH:52]=[C:31]([O:30][CH3:29])[CH:32]=4)=[CH:38][CH:39]=3)[CH2:47][CH2:46]2)=[O:28])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=2)=[CH:11][N:10]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 67327442HCID 67327442, compoundHCID 67327483HCID 67327483, compound

Product 1

HCID 53361692HCID 53361692, compoundYield 103.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (E)-3-[3-chloro-4-({5-[(4-fluorobenzyl)oxy]pyridin-2-yl}oxy)phenyl]prop-2-enoic acid (212 mg) in DMF (7.0 mL) were added 1-{4-[2-(3-methoxyphenoxy)ethyl]benzyl}piperazine (190 mg), HOBT (89 mg) and WSC (112 mg) at room temperature, then the reaction mixture was stirred over night. The reaction mixture was basified with saturated aqueous NaHCO3, extracted with AcOEt. The organic layer was washed with water and saturated aqueous NaCl, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=1/4 to 0/1 and then MeOH/AcOEt=1/9) to afford (E)-3-[3-chloro-4-({5-[(4-fluorobenzyl)oxy]pyridin-2-yl}oxy)phenyl]-1-(4-{4-[2-(3-methoxyphenoxy)ethyl]benzyl}-piperazin-1-yl)prop-2-en-1-one (387 mg) as a colorless amorphous. To a solution of that amorphous (387 mg) in AcOEt (7.0 mL) was added 6 M aqueous HCl (0.088 mL) at room temperature, and then the reaction mixture was stirred for 30 minutes. The reaction mixture was filtered off, and the crude crystal was recrystallized from EtOH—H2O to afford (E)-3-[3-chloro-4-({5-[(4-fluorobenzyl)oxy]pyridin-2-yl}oxy)phenyl]-1-(4-{4-[2-(3-methoxyphenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one hydrochloride as a colorless powder (333 mg).

Workup

  1. extractionextracted with AcOEt
  2. washThe organic layer was washed with water and saturated aqueous NaCl
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (n-hexane/AcOEt=1/4 to 0/1

Sources & evidence

ORD record
ord-3a971cfe36d040c1bb05ddd939ec6d9a
Source dataset
uspto-grants-2014_05
Patent number
US08722663B2

Reaction notes

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