1-Hydroxybenzotriazole → (2R)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzamido}-2-[p-(carboxy-methyl)phenyl]acetic acid

HRID 1289243Notes

Reaction equation

HRID 1289243 reaction equation
[NH2:1][C@H:2]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=[O:14])=[CH:8][CH:7]=1)[C:3]([OH:5])=[O:4].C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[F:28][C:29]1[CH:48]=[C:47]([N:49]([CH3:73])[CH:50]2[C:54]3[CH:55]=[C:56]4[C:61](=[CH:62][C:53]=3[CH2:52][CH2:51]2)[N:60]=[C:59]([CH3:63])[N:58]([CH2:64][O:65][C:66](=[O:71])[C:67]([CH3:70])([CH3:69])[CH3:68])[C:57]4=[O:72])[CH:46]=[CH:45][C:30]=1[C:31](OC1C(F)=C(F)C(F)=C(F)C=1F)=[O:32].ON1C2C=CC=CC=2N=N1>>[F:28][C:29]1[CH:48]=[C:47]([N:49]([CH3:73])[CH:50]2[C:54]3[CH:55]=[C:56]4[C:61](=[CH:62][C:53]=3[CH2:52][CH2:51]2)[N:60]=[C:59]([CH3:63])[N:58]([CH2:64][O:65][C:66](=[O:71])[C:67]([CH3:68])([CH3:69])[CH3:70])[C:57]4=[O:72])[CH:46]=[CH:45][C:30]=1[C:31]([NH:1][C@H:2]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=[O:14])=[CH:8][CH:7]=1)[C:3]([OH:5])=[O:4])=[O:32]

Participants

5

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 11708267BistrimethylsilylacetamidHCID 19066320Pentafluorophenyl o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoateHCID 54357908(R)-alpha-amino-p-carboxymethylphenylacetic acid

Product 1

HCID 22885368(2R)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzamido}-2-[p-(carboxy-methyl)phenyl]acetic acidYield 70.6%

Procedure

A solution of (R)-α-amino-p-carboxymethylphenylacetic acid (0.1 g, 0.48 mmol) and bis trimethylsilyl acetamide (0.195 g, 0.96 mmol in 5 ml of DMF) was stirred for 20 minutes at room temperature. To the solution was then added pentafluorophenyl o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivalyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzoate (0.213 g, 0.4 mmol), prepared as described in Example 2, followed by N-hydroxybenzotriazole (10 mg) and the stirring was maintained for a further 5 hours. The reaction mixture was then evaporated to dryness and the crude material redissolved in ether. The ether layers were extracted with NaHCO3. The aqueous layers were acidified to pH 2.5 with 2N HCl and the precipiate was filtered off, washed with water and dried under vacuum to give (2R)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-4-oxo-3-pivaloyloxymethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]benzamido}-2-[p-(carboxy-methyl)phenyl]acetic acid (0.19 g), 85%) as a white solid;

Workup

  1. temperaturethe stirring was maintained for a further 5 hours
  2. customThe reaction mixture was then evaporated to dryness
  3. dissolutionthe crude material redissolved in ether
  4. extractionThe ether layers were extracted with NaHCO3
  5. filtrationthe precipiate was filtered off
  6. washwashed with water
  7. customdried under vacuum

Sources & evidence

ORD record
ord-b313fd722f8b4ee2acf741ab20e38f2c
Source dataset
uspto-grants-1998_05
Patent number
US05747499

Reaction notes

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