Potassium Carbonate → Ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-(3-morpholinopropoxy)phenyl)-1H-pyrrole-2-carboxylate

HRID 1507735Notes

Reaction equation

HRID 1507735 reaction equation
[CH2:1]([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:22](=[O:26])[N:23]([CH3:25])[CH3:24])[N:11]([C:27]2[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=2)[C:10]=1[C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl[CH2:41][CH2:42][CH2:43][N:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:1]([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:22](=[O:26])[N:23]([CH3:25])[CH3:24])[N:11]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH2:41][CH2:42][CH2:43][N:44]3[CH2:49][CH2:48][O:47][CH2:46][CH2:45]3)=[CH:29][CH:28]=2)[C:10]=1[C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 122962834-(3-Chloropropyl)morpholinium chlorideHCID 117642662Ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-hydroxyphenyl)-1H-pyrrole-2-carboxylate

Product 1

HCID 117642460Ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-(3-morpholinopropoxy)phenyl)-1H-pyrrole-2-carboxylateYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-hydroxyphenyl)-1H-pyrrole-2-carboxylate (36) (45 mg, 0.09 mmol), 4-(3-chloropropyl)morpholine hydrochloride (19 mg, 0.10 mmol) and K2CO3 (25 mg, 0.18 mmol) in DMF (1 mL) was stirred at 60° C. for 18 h. The reaction mixture was partitioned between EtOAc (10 mL) and water (5 mL), the organic layer was separated and washed with brine (5 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in MeOH (2 mL) and loaded onto a column of SCX (5 g). The column was washed with MeOH and then the product was eluted with 1% NH3 in MeOH, removal of the solvents in vacuo afforded ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-(3-morpholinopropoxy)phenyl)-1H-pyrrole-2-carboxylate (37) (32 mg, 57%) as a yellow oil: m/z 642 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 7.47-7.42 (m, 2H), 7.41-7.30 (m, 8H), 7.10-7.05 (m, 2H), 6.99-6.91 (m, 2H), 5.11 (s, 2H), 4.96 (s, 2H), 4.04-3.95 (m, 4H), 3.59-3.52 (m, 5H), 2.72-2.67 (m, 6H), 2.44-2.38 (m, 3H), 2.37-2.32 (m, 5H), 1.92-1.81 (m, 2H), 1.00 (t, J=7.0 Hz, 3H).

Workup

  1. customThe reaction mixture was partitioned between EtOAc (10 mL) and water (5 mL)
  2. customthe organic layer was separated
  3. washwashed with brine (5 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in MeOH (2 mL)
  8. washThe column was washed with MeOH
  9. washthe product was eluted with 1% NH3 in MeOH, removal of the solvents in vacuo

Sources & evidence

ORD record
ord-68854e0616ce4ef58db42dfaf602490e
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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