Bromide ion → HCID 57857123, compound

HRID 1643320Notes

Reaction equation

HRID 1643320 reaction equation
[NH2:1][C:2]1[CH:29]=[CH:28][C:5]([C:6]([NH:8][C:9]2[CH:14]=[C:13]([C:15]3[CH:19]=[CH:18][S:17][CH:16]=3)[CH:12]=[CH:11][C:10]=2[NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:7])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39].[Na+].[I-].[Br-]>CC#N>[C:23]([O:22][C:21]([NH:20][C:10]1[CH:11]=[CH:12][C:13]([C:15]2[CH:19]=[CH:18][S:17][CH:16]=2)=[CH:14][C:9]=1[NH:8][C:6]([C:5]1[CH:28]=[CH:29][C:2]([NH:1][CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])=[CH:3][CH:4]=1)=[O:7])=[O:27])([CH3:24])([CH3:25])[CH3:26]

Participants

7

Reactant 5

HCID 259Bromide ionHCID 5238Sodium Iodide2×HCID 11430Potassium CarbonateHCID 79177tert-Butyl bromoacetateHCID 68985357HCID 68985357, compound

Product 1

HCID 57857123HCID 57857123, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of tert-butyl [2-[(4-aminobenzoyl)amino]-4-(3-thienyl)phenyl]carbamate (945 mg, 2.31 mmol) in CH3CN (5.0 mL) was added K2CO3 (639 mg, 4.62 mmol), tert-butyl bromoacetate (1.35 mL, 9.24 mmol), and NaI (139 mg, 0.92 mmol). The reaction mixture was heated at reflux for 12 hours and an additional portion of bromide and NaI were added to obtain mono and bis alkylated product. The reaction was cooled to room temperature, filtered and the organic layer was concentrated in vacuo. The crude residue was purified by reverse-phase chromatography (10-100% MeCN/H2O with 0.05% TFA) to separate mono and bis alkylated product (ratio of mono to bis is ˜1:2). The appropriate fractions were combined, diluted with EtOAc (20 mL) and washed with sat.'d aq. NaHCO3 (1×10 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo and gave the desired tert-butyl {[4-({[2-[(tert-butoxycarbonyl)amino]-5-(3-thienyl)phenyl]amino}carbonyl)phenyl]amino}acetate which was confirmed MS: cal'd 524.2 (MH+), exp 524.2 (MH+).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 12 hours
  3. customto obtain mono
  4. filtrationfiltered
  5. concentrationthe organic layer was concentrated in vacuo
  6. customThe crude residue was purified by reverse-phase chromatography (10-100% MeCN/H2O with 0.05% TFA)
  7. customto separate mono
  8. additiondiluted with EtOAc (20 mL)
  9. washwashed with sat.'d aq. NaHCO3 (1×10 mL)
  10. dry with materialThe organic layer was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6c42fea3e5404f7da1c00df9984a2bbe
Source dataset
uspto-grants-2012_02
Patent number
US08119685B2

Reaction notes

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