Tetrahydrofuran → 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-phenoxycarbonylaminophenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester

HRID 2280287Notes

Reaction equation

HRID 2280287 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][C:7]1[N:8]([C:19]2[CH:24]=[CH:23][C:22]([C:25](=[O:27])[NH2:26])=[CH:21][C:20]=2[CH3:28])[C:9]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)=[CH:10][CH:11]=1)[CH3:2].CCN([CH:36]([CH3:38])[CH3:37])C(C)C.C1(N[C:46](=[O:48])[O-:47])C=CC=CC=1.[CH2:49]1[CH2:53]OC[CH2:50]1>C(Cl)Cl.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][C:7]1[N:8]([C:19]2[CH:24]=[CH:23][C:22]([C:25](=[O:27])[NH2:26])=[CH:21][C:20]=2[CH3:28])[C:9]([C:12]2[CH:13]=[CH:14][C:15]([NH:18][C:46]([O:48][C:37]3[CH:36]=[CH:38][CH:53]=[CH:49][CH:50]=3)=[O:47])=[CH:16][CH:17]=2)=[CH:10][CH:11]=1)[CH3:2]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 21896570PhenylcarbamateHCID 583056233-[5-(4-aminophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl]propanoic acid ethyl ester

Product 1

HCID 583056243-[1-(4-carbamoyl-2-methylphenyl)-5-(4-phenoxycarbonylaminophenyl)-1H-pyrrol-2-yl]-propionic acid ethyl esterYield 48%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, 3-[5-(4-aminophenyl)-1-(4-carbamoyl-2-methylphenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (11A, synthesis described in Scheme 4 where R1=4-carbamoyl-2-methylphenyl) (106 mg, 0.26 mmol) was dissolved in 1 mL methylene chloride. The mixture was cooled in an ice bath. Hünig's base (0.12 mL, 0.65 mmol) was added. Phenylcarbamate (0.05 mL, 0.39 mmol) was added dropwise. The reaction was stirred at 0° C. for 30 min, and then allowed to warm to room temperature. After 24 hrs, 3 mL THF/3 mL sodium bicarbonate was added and stirred for 40 min. Then ethyl acetate (3 mL) was added and the layers separated. The aqueous layer was further extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by preparative TLC plate (1500 microns, 5% MeOH/CH2Cl2). The desired band (rf=0.51) was isolated and dried under high vacuum to yield 3-[1-(4-carbamoyl-2-methylphenyl)-5-(4-phenoxycarbonylaminophenyl)-1H-pyrrol-2-yl]-propionic acid ethyl ester (13B) (66 mg, 48%, hygroscopic tan powder).

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. temperatureto warm to room temperature
  3. waitAfter 24 hrs
  4. stirringstirred for 40 min
  5. customthe layers separated
  6. extractionThe aqueous layer was further extracted with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified by preparative TLC plate (1500 microns, 5% MeOH/CH2Cl2)
  12. customThe desired band (rf=0.51) was isolated
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-e98ac9b969fc42dd80ae2d3270aa554e
Source dataset
uspto-grants-2015_09
Patent number
US09138427B2

Reaction notes

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