Diisopropylethylamine → (R)-3-benzoylamino-3-(4-{3-methoxy-4-[3-(2-methylphenyl)ureido]-phenylacetyl-amino}-phenyl)-propanoic acid methyl ester

HRID 1018000Notes

Reaction equation

HRID 1018000 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([OH:23])=O)[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:57][O:58][C:59](=[O:78])[CH2:60][C@@H:61]([NH:69][C:70](=[O:77])[C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1)[C:62]1[CH:67]=[CH:66][C:65]([NH2:68])=[CH:64][CH:63]=1>CN(C)C=O>[CH3:57][O:58][C:59](=[O:78])[CH2:60][C@@H:61]([NH:69][C:70](=[O:77])[C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1)[C:62]1[CH:63]=[CH:64][C:65]([NH:68][C:21](=[O:23])[CH2:20][C:5]2[CH:6]=[CH:7][C:8]([NH:9][C:10]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[CH3:19])=[O:11])=[C:3]([O:2][CH3:1])[CH:4]=2)=[CH:66][CH:67]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114498403-Methoxy-4-o-tolylureidophenylacetic acidHCID 54167804(R)-3-benzoylamino-3-(4-aminophenyl)-propanoic acid methyl ester

Product 1

HCID 54019509(R)-3-benzoylamino-3-(4-{3-methoxy-4-[3-(2-methylphenyl)ureido]-phenylacetyl-amino}-phenyl)-propanoic acid methyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 3-methoxy-4-[3-(2-methylphenyl)ureido]phenylacetic acid (1.52 g, prepared as described in Reference Example 31) in anhydrous dimethylformamide (40 ml), under an atmosphere of argon, was treated sequentially with O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (1.84 g), diisopropylethylamine (3.4 ml) and a solution of (R)-3-benzoylamino-3-(4-aminophenyl)-propanoic acid methyl ester [2.0 g, Reference Example 13(a)] in dimethylformamide (10 ml). After stirring for 45 minutes at ambient temperature the reaction mixture was evaporated. The residue was treated with water (150 ml) and hydrochloric acid (10 ml, 1M) was added to the aqueous slurry. The mixture was filtered and the insoluble material was washed three times with water (50 ml) then dried in vacuo to give the title compound as white solid (2.53 g).

Workup

  1. customwas evaporated
  2. additionThe residue was treated with water (150 ml) and hydrochloric acid (10 ml, 1M)
  3. additionwas added to the aqueous slurry
  4. filtrationThe mixture was filtered
  5. washthe insoluble material was washed three times with water (50 ml)
  6. customthen dried in vacuo

Sources & evidence

ORD record
ord-40d9f87cbb9646dd8c2e18cfb7c47f7f
Source dataset
uspto-grants-2002_11
Patent number
US06479519B1

Reaction notes

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