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

HRID 1289241Notes

Reaction equation

HRID 1289241 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].[F:16][C:17]1[CH:36]=[C:35]([N:37]([CH3:61])[CH:38]2[C:42]3[CH:43]=[C:44]4[C:49](=[CH:50][C:41]=3[CH2:40][CH2:39]2)[N:48]=[C:47]([CH3:51])[N:46]([CH2:52][O:53][C:54](=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[C:45]4=[O:60])[CH:34]=[CH:33][C:18]=1[C:19](OC1C(F)=C(F)C(F)=C(F)C=1F)=[O:20].CN1CCOCC1.ON1C2C=CC=CC=2N=N1.Cl>CN(C=O)C.CO.O>[F:16][C:17]1[CH:36]=[C:35]([N:37]([CH3:61])[CH:38]2[C:42]3[CH:43]=[C:44]4[C:49](=[CH:50][C:41]=3[CH2:40][CH2:39]2)[N:48]=[C:47]([CH3:51])[N:46]([CH2:52][O:53][C:54](=[O:59])[C:55]([CH3:56])([CH3:57])[CH3:58])[C:45]4=[O:60])[CH:34]=[CH:33][C:18]=1[C:19]([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:20]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 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 54357909(S)-alpha-amino-p-carboxymethylphenylacetic acid

Product 1

HCID 15294191(2S)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-3-pivaloyloxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzamido}-2-[p-(carboxymethyl)phenyl]acetic acidYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a solution of (S)-α-amino-p-carboxymethylphenylacetic acid (0.1 g, 0.48 mmol) and pentafluorophenyl 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]-benzoate (0.213 g, 0.4 mmol), prepared as described in Example 2, in 5 ml of DMF was added bistrimethyl silyl acetamide (BSA) (0.194 g, 0.96 mmol). After stirring under N2 for 20 minutes N-methylmorpholine was added (0.081 g, 0.8 mmol) followed by N-hydroxybenzotriazole (HOBT) (0.01 g). The reaction mixture was stirred at room temperature for 4 hours and evaporated to dryness. The solid obtained by trituration with ether and filtration was resuspended in a mixture of methanol/water (2 ml) and the pH adjusted to 2.5 with 2N HCl . The resulting precipitate was filtered off, washed with water and dried to give (2S)-2-{o-fluoro-p-[N-methyl-N-((6RS)-2-methyl-3-pivaloyloxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl)amino]-benzamido}-2-[p-(carboxymethyl)phenyl]acetic acid (140 mg, 64%) as a yellow solid;

Workup

  1. additionwas added (0.081 g, 0.8 mmol)
  2. customevaporated to dryness
  3. customThe solid obtained by trituration with ether and filtration
  4. filtrationThe resulting precipitate was filtered off
  5. washwashed with water
  6. customdried

Sources & evidence

ORD record
ord-bf319897378e4a9aa44c6c885a643c6d
Source dataset
uspto-grants-1998_05
Patent number
US05747499

Reaction notes

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