4-Methylmorpholine → HCID 89625018, compound

HRID 1507737Notes

Reaction equation

HRID 1507737 reaction equation
Cl[C:2]([O:4][CH2:5][CH:6]([CH3:8])C)=O.[CH3:9][O:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14].CN1CC[O:20]CC1.[CH3:23][N:24]([CH3:47])[C:25]([C:27]1[N:31]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[C:30]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:29]([OH:45])[C:28]=1O)=[O:26]>C(Cl)Cl>[CH3:9][O:10][CH2:11][CH2:12][C:13]([O:15][C:28]1[C:29]([O:45][C:8](=[O:20])[CH2:6][CH2:5][O:4][CH3:2])=[C:30]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[N:31]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[C:27]=1[C:25](=[O:26])[N:24]([CH3:23])[CH3:47])=[O:14]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 1344423-Methoxypropionic acidHCID 71576576HCID 71576576, compound

Product 1

HCID 89625018HCID 89625018, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Isobutyl chloroformate (410 μL, 3.16 mmol) was added dropwise to a stirred solution of 3-methoxypropanoic acid (297 μL, 3.16 mmol) and 4-methylmorpholine (790 μL, 7.18 mmol) in DCM (20 mL) at −15° C. and the reaction mixture was allowed to stir for 20 min. A solution of ethyl 5-(dimethylcarbamoyl)-3,4-dihydroxy-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate (UL1-012) (0.5 g, 1.44 mmol) in DCM (20 mL) was added, and the reaction allowed to warm to RT and stirred for 18 h. The solvents were removed in vacuo, and the mixture was partitioned between DCM (30 mL) and 1 M HCl (aq.) (10 mL), the organic layer was separated and washed with sat. NaHCO3 (aq.) (10 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography (40 g, 50-70% EtOAc in isohexane) to afford 2-(dimethylcarbamoyl)-5-(ethoxycarbonyl)-1-(4-methoxyphenyl)-1H-pyrrole-3,4-diyl bis(3-methoxypropanoate) (UL1-104) (300 mg, 39%) as a yellow oil: m/z 521 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 7.24-7.15 (m, 2H), 6.98-6.89 (m, 2H), 4.00 (q, J=7.1 Hz, 2H), 3.79 (s, 3H), 3.65-3.59 (m, 4H), 3.27 (s, 3H), 3.25 (s, 3H), 2.82 (s, 3H), 2.78 (t, J=6.0 Hz, 4H), 2.71 (s, 3H), 1.05 (t, J=7.1 Hz, 3H).

Workup

  1. stirringstirred for 18 h
  2. customThe solvents were removed in vacuo
  3. customthe mixture was partitioned between DCM (30 mL) and 1 M HCl (aq.) (10 mL)
  4. customthe organic layer was separated
  5. washwashed with sat. NaHCO3 (aq.) (10 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified by silica gel chromatography (40 g, 50-70% EtOAc in isohexane)

Sources & evidence

ORD record
ord-e9faa6bf5cd341c697e57bf18918e087
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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