Water → HCID 68748525, compound

HRID 1047116Notes

Reaction equation

HRID 1047116 reaction equation
C([O:8][P:9]([O:19][CH2:20][CH2:21][N:22]1[C:31]2[C:26](=[CH:27][C:28]([C:32]3[CH:33]=[N:34][C:35]([NH:47][C:48](=[O:52])[NH:49][CH2:50][CH3:51])=[CH:36][C:37]=3[C:38]3[S:39][CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[N:42]=3)=[CH:29][N:30]=2)[C:25](=[O:53])[C:24]([C:54]([OH:56])=[O:55])=[CH:23]1)([O:11]CC1C=CC=CC=1)=[O:10])C1C=CC=CC=1.C[Si](Br)(C)C.O>ClCCl.CO>[CH2:50]([NH:49][C:48]([NH:47][C:35]1[N:34]=[CH:33][C:32]([C:28]2[CH:27]=[C:26]3[C:31](=[N:30][CH:29]=2)[N:22]([CH2:21][CH2:20][O:19][P:9]([OH:11])([OH:10])=[O:8])[CH:23]=[C:24]([C:54]([OH:56])=[O:55])[C:25]3=[O:53])=[C:37]([C:38]2[S:39][CH:40]=[C:41]([C:43]([F:45])([F:46])[F:44])[N:42]=2)[CH:36]=1)=[O:52])[CH3:51]

Participants

6

Reactant 3

HCID 962WaterHCID 76113BromotrimethylsilaneHCID 68746318HCID 68746318, compound

Product 1

HCID 68748525HCID 68748525, compoundYield 26.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-(2-{[bis(benzyloxy)phosphoryl]oxy}ethyl)-6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (Example 13, 220 mg, 0.27 mmol) was dissolved in dry dichloromethane (30 mL), the reaction mixture was cooled to 0° C. Trimethylsilyl bromide (83.31 mg, 0.54 mmol) was added and the mixture was stirred for 2 h at room temperature. A solid formed on the walls of round bottom flask. The solvent was decanted and the solid was washed with ethyl acetate (20 mL) to give crude compound. The crude compound was dissolved in methanol (20 mL) and water (50 mL) was added to precipitate a solid compound which was filtered and dried to give crude compound. The crude compound was purified preparative HPLC to afford 45 mg (25.9%) of 6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-4-oxo-1-[2-(phosphonooxy)ethyl]-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid.

Workup

  1. customA solid formed on the walls of round bottom flask
  2. customThe solvent was decanted
  3. washthe solid was washed with ethyl acetate (20 mL)
  4. customto give crude compound
  5. customto precipitate a solid compound which
  6. filtrationwas filtered
  7. customdried
  8. customto give crude compound
  9. customThe crude compound was purified preparative HPLC

Sources & evidence

ORD record
ord-81ce8c21fc8042a4a550865a740078a6
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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