Methyl iodide → HCID 91084433, compound

HRID 1393067Notes

Reaction equation

HRID 1393067 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[NH2:22][C:23]1[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:24]=1[C:25](O)=[O:26].C(Cl)CCl.Cl.C1C=CC2N(O)N=NC=2C=1.[C:48](N1C=CN=C1)(N1C=CN=C1)=[O:49].CI.[C:62](=O)([O-])[O-].[K+].[K+]>O.C(OCC)(=O)C.CN(C=O)C.O1CCCC1.C(N(CC)CC)C>[CH3:1][O:2][C:3](=[O:21])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:25](=[O:26])[C:24]3[C:23](=[CH:31][CH:30]=[C:29]([I:32])[CH:28]=3)[N:22]([CH3:62])[C:48]2=[O:49])=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:7]

Participants

13

Reactant 7

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 682631,1'-CarbonyldiimidazoleHCID 72911Benzoic acid, 2-amino-5-iodo-HCID 757711-HydroxybenzotriazoleHCID 110118554-Amino-N-((1,1-dimethylethoxy)carbonyl)-L-phenylalanine methyl esterHCID 22619321HCID 22619321, compound

Product 1

HCID 91084433HCID 91084433, compoundYield 74.3%

Reagents, catalysts & solvents 5

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
40 °C

Procedure

The mixture of N-(t-butoxycarbonyl)-4-amino-L-phenylalanine methylester(10.25 g), 2-amino-5-iodobenzoic acid (9.18 g), EDC/HCl (6.8 g), HOBT (4.8 g), triethylamine (6.6 mL) and tetrahydrofuran (300 mL) was stirred at 40° C. overnight. The solution wherein about a half amount of the solvent was removed was diluted with water and ethyl acetate and liquid separation was conducted. The organic layer was washed with water, saturated aqueous solution of ammonium chloride, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was removed to obtain 22 g of the crude material. The crude material (22 g), CDI (carbonyldiimidazole) (17 g) and DMF (200 mL) were stirred at 80° C. overnight. The reaction solution was diluted with water and ethyl acetate, and liquid separation was conducted. The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was removed to obtain 23.4 g of the crude material. The crude material (23.4 g), methyl iodide (3 mL), potassium carbonate (10.0 g) and DMF (100 mL) were stirred at room temperature overnight. The reaction solution was diluted with water and ethyl acetate, and liquid separation was conducted. The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was removed to obtain 15 g of the intended compound.

Workup

  1. customThe solution wherein about a half amount of the solvent was removed
  2. additionwas diluted with water and ethyl acetate and liquid separation
  3. washThe organic layer was washed with water, saturated aqueous solution of ammonium chloride, saturated aqueous solution of sodium hydrogen carbonate and saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed
  6. customto obtain 22 g of the crude material
  7. washThe organic layer was washed with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was removed
  10. customto obtain 23.4 g of the crude material
  11. washThe organic layer was washed with water
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThe solvent was removed

Sources & evidence

ORD record
ord-b2fbbf13ea404c4295e9852aaf7ad02b
Source dataset
uspto-grants-2008_03
Patent number
US07345049B2

Reaction notes

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