1,1'-Carbonyldiimidazole → HCID 86657120, compound

HRID 468591Notes

Reaction equation

HRID 468591 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[N:4]=[C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C@H:15]([CH3:19])[C:16]([OH:18])=O)=[CH:11][CH:10]=2)[S:6][CH:7]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[CH3:35][O:36][C:37](=[O:41])[C@@H:38]([CH3:40])[NH2:39]>C(Cl)Cl>[F:20][C:2]([F:1])([F:21])[C:3]1[N:4]=[C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([C@H:15]([CH3:19])[C:16]([NH:39][C@H:38]([CH3:40])[C:37]([O:36][CH3:35])=[O:41])=[O:18])=[CH:13][CH:14]=2)[S:6][CH:7]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 11182647Methyl D-alaninate hydrochlorideHCID 45110932HCID 45110932, compound

Product 1

HCID 86657120HCID 86657120, compoundYield 78.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A cooled solution of (2S)-2-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)propanoic acid (3) (0.1 g, 0.32 mmol) and CDI (0.054 g, 0.33 mmol) in dry CH2Cl2 (5 mL) was stirred for 1 h at T=0-5° C. After ice-water bath removal, a mixture of D-alanine methyl ester hydrochloride (0.045 g, 0.32 mmol) and TEA (90 μl, 0.65 mmol) was added with vigorous stirring and the resulting mixture was stirred overnight at room temperature. At the complete disappearance of the starting material, a buffer H3PO4/H2PO4− solution (pH=2.0, 5 ml) was added and the reaction mixture was transferred into a separatory funnel. The two phases were separated and the organic one washed with the same buffer (3×5 mL), dried over Na2SO4 and evaporated under vacuum to give a crude which was purified by flash chromatography. Pure methyl (2R)-2-{[(2S)-2-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)propanoyl]amino}propanoate (0.1 g, 0.25 mmol) was isolated as a yellow oil (78%).

Workup

  1. customAfter ice-water bath removal
  2. additionwas added
  3. stirringthe resulting mixture was stirred overnight at room temperature
  4. customthe reaction mixture was transferred into a separatory funnel
  5. customThe two phases were separated
  6. washthe organic one washed with the same buffer (3×5 mL)
  7. dry with materialdried over Na2SO4
  8. customevaporated under vacuum
  9. customto give a crude which
  10. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-f0d864a1af7945688fa9d501c1cbb2d7
Source dataset
uspto-grants-2014_01
Patent number
US08624036B2

Reaction notes

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