4-Iodoaniline → 4-{[(4-tert-Butyl-phenyl)-(4-iodo-phenylcarbamoyl)-methyl]-amino}-benzoic Acid Tert-butyl Ester

HRID 2371263Notes

Reaction equation

HRID 2371263 reaction equation
[C:1]([O:5][C:6](=[O:28])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:20][CH:19]=2)[C:15]([OH:17])=O)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[I:50][C:51]1[CH:57]=[CH:56][C:54]([NH2:55])=[CH:53][CH:52]=1.CCN(C(C)C)C(C)C>CN(C=O)C.O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:28])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH:14]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([CH3:25])([CH3:27])[CH3:26])=[CH:20][CH:19]=2)[C:15](=[O:17])[NH:55][C:54]2[CH:56]=[CH:57][C:51]([I:50])=[CH:52][CH:53]=2)=[CH:9][CH:8]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

9

Reactant 5

HCID 108934-IodoanilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 674862324-{[(4-tert-Butyl-phenyl)-carboxy-methyl]-amino}-benzoic Acid Tert-butyl Ester

Product 1

HCID 674865594-{[(4-tert-Butyl-phenyl)-(4-iodo-phenylcarbamoyl)-methyl]-amino}-benzoic Acid Tert-butyl EsterYield 70%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4-{[(4-tert-Butyl-phenyl)-carboxy-methyl]-amino}-benzoic acid tert-butyl ester (760 mg, 2.0 mmol), was taken up in 5 mL of DMF followed by addition of HOBt (765 mg, 5.0 mmol) and EDCI (958 mg, 5.0 mmol). The reaction was stirred at RT for 30 min, 4-iodoaniline (657 mg, 3 mmol) was added followed by Hunig's base (640 mg, 5 mmol) and allowed to stir an additional 16 h at RT. Ethyl acetate (20 mL) and 20 mL water were added and separated. The aqueous layer was then back extracted with another 10 mL of EtOAc, the organic layer were combined and washed with water (3×20 mL). The organic layer was dried over sodium sulfate, filtered and the solvent was removed under reduced pressure to give a brown solid. The solids were triturated with methanol to give a white solid (818 mg, 70%). 1H NMR (CDCl3): δ 1.32 (9H, s), 1.58 (9H, s), 4.89 (2H, d), 5.02 (1H, d), 6.62 (2H, d, J=8.4 Hz), 7.22-7.95 (10H, m), 8.81 (1H, s).

Workup

  1. stirringto stir an additional 16 h at RT
  2. customseparated
  3. extractionThe aqueous layer was then back extracted with another 10 mL of EtOAc
  4. washwashed with water (3×20 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customto give a brown solid
  9. customThe solids were triturated with methanol

Sources & evidence

ORD record
ord-f941b76df3b24e92a96acb2d865c752b
Source dataset
uspto-grants-2014_04
Patent number
US08710236B2

Reaction notes

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