Bromotrimethylsilane → HCID 68752437, compound

HRID 1047126Notes

Reaction equation

HRID 1047126 reaction equation
C([O:8][P:9]([O:12][CH2:13][C@@H:14]([N:19]1[C:28]2[C:23](=[CH:24][C:25]([C:29]3[CH:30]=[N:31][C:32]([NH:44][C:45](=[O:49])[NH:46][CH2:47][CH3:48])=[CH:33][C:34]=3[C:35]3[S:36][CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[N:39]=3)=[CH:26][N:27]=2)[C:22](=[O:50])[C:21]([C:51]([OH:53])=[O:52])=[CH:20]1)[CH2:15][CH:16]([CH3:18])[CH3:17])([OH:11])=[O:10])C1C=CC=CC=1.C[Si](Br)(C)C>ClCCl>[CH2:47]([NH:46][C:45]([NH:44][C:32]1[N:31]=[CH:30][C:29]([C:25]2[CH:24]=[C:23]3[C:28](=[N:27][CH:26]=2)[N:19]([C@@H:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:13][O:12][P:9]([OH:11])([OH:10])=[O:8])[CH:20]=[C:21]([C:51]([OH:53])=[O:52])[C:22]3=[O:50])=[C:34]([C:35]2[S:36][CH:37]=[C:38]([C:40]([F:41])([F:43])[F:42])[N:39]=2)[CH:33]=1)=[O:49])[CH3:48]

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 68751172HCID 68751172, compound

Product 1

HCID 68752437HCID 68752437, compoundYield 35.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-[(2S)-1-{[(Benzyloxy)(hydroxy)phosphoryl]oxy}-4-methylpentan-2-yl]-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 24, 700 mg, 0.90 mmol) was dissolved in dry dichloromethane (30 mL), then the reaction mixture was cooled to 0° C. Trimethylsilyl bromide (TMS-Br) (0.55 g, 3.61 mmol) was added and the mixture was stirred for 2 h at room temperature. A solid formed on the walls of the round bottom flask, and the solvent was decanted. The solid was washed with ethyl acetate (20 mL) then dissolved in methanol (20 mL) and water (50 mL) was added to precipitate a solid which was filtered and dried to give crude compound (380 mg). The crude compound was purified by preparative HPLC to afford 220 mg (25.9%) of 6-{6-[(ethylcarbamoyl)amino]-4-[4-(trifluoromethyl)-1,3-thiazol-2-yl]pyridin-3-yl}-1-[(2S)-4-methyl-1-(phosphonooxy)pentan-2-yl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid.

Workup

  1. customA solid formed on the walls of the round bottom flask
  2. customthe solvent was decanted
  3. washThe solid was washed with ethyl acetate (20 mL)
  4. dissolutionthen dissolved in methanol (20 mL)
  5. additionwater (50 mL) was added
  6. customto precipitate a solid which
  7. filtrationwas filtered
  8. customdried
  9. customto give crude compound (380 mg)
  10. customThe crude compound was purified by preparative HPLC

Sources & evidence

ORD record
ord-35235ec54b7f4b689facec74462745a5
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

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