Chlorotrimethylsilane → Tert-butyl 3-(2-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-6-{[(methylsulfonyl)-amino]carbonyl}-7-oxo-7,8-dihydro-1,8-naphthyridin-4-yl)-1-piperidinecarboxylate

HRID 412309Notes

Reaction equation

HRID 412309 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].C(N(CC)CC)C.C[Si](Cl)(C)C.CNC1(NC)C=CN=CC1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[C:55]([O:59][C:60]([N:62]1[CH2:67][CH2:66][CH2:65][CH:64]([C:68]2[CH:77]=[C:76]([C:78]3[C:83]([O:84][CH2:85][C:86]4[CH:91]=[CH:90][C:89]([O:92][CH3:93])=[CH:88][CH:87]=4)=[CH:82][CH:81]=[CH:80][C:79]=3[O:94][CH2:95][CH:96]3[CH2:98][CH2:97]3)[N:75]=[C:74]3[C:69]=2[CH:70]=[C:71]([C:100](O)=[O:101])[C:72](=[O:99])[NH:73]3)[CH2:63]1)=[O:61])([CH3:58])([CH3:57])[CH3:56]>C1(C)C=CC=CC=1>[CH:96]1([CH2:95][O:94][C:79]2[CH:80]=[CH:81][CH:82]=[C:83]([O:84][CH2:85][C:86]3[CH:91]=[CH:90][C:89]([O:92][CH3:93])=[CH:88][CH:87]=3)[C:78]=2[C:76]2[CH:77]=[C:68]([CH:64]3[CH2:65][CH2:66][CH2:67][N:62]([C:60]([O:59][C:55]([CH3:58])([CH3:56])[CH3:57])=[O:61])[CH2:63]3)[C:69]3[CH:70]=[C:71]([C:100]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[O:101])[C:72](=[O:99])[NH:73][C:74]=3[N:75]=2)[CH2:98][CH2:97]1

Participants

8

Reactant 6

HCID 6397ChlorotrimethylsilaneHCID 8471Triethylamine2×HCID 72879MethanesulfonamideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 222589325-[1-(Tert-butoxycarbonyl)-3-piperidinyl]-7-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylic acidHCID 865890494,4-Dimethylaminopyridine

Product 1

HCID 22258982Tert-butyl 3-(2-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-6-{[(methylsulfonyl)-amino]carbonyl}-7-oxo-7,8-dihydro-1,8-naphthyridin-4-yl)-1-piperidinecarboxylateYield 43.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of methanesulfonamide (0.026 g, 0.268 mmol) and triethylamine (0.030 mL, 0.229 mmol) in toluene (2 mL) was added trimethylsilyl chloride (0.020 mL, 0.152 mmol). The mixture was stirred at 90° C. for 1 hr, and then concentrated under reduced pressure. To the residue diluted with dichloromethane (2 mL) were added triethylamine (0.020 mL, 0.152 mmol), 4,4-dimethylaminopyridine (0.002 g, 0.015 mmol), benzotriazole-1-yloxy-tris(dimethylamino)phosphonium hexafluoro-phosphate (0.040 g, 0.091 mmol) and 5-[1-(tert-butoxycarbonyl)-3-piperidinyl]-7-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylic acid (0.050 g, 0.076 mmol) successively. The mixture was stirred at room temperature for 6 hrs. The mixture was extracted with ethyl acetate and water. The separated organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by preparative TLC (hexane/ethyl acetate=1/1×2) to give tert-butyl 3-(2-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-6-{[(methylsulfonyl)-amino]carbonyl}-7-oxo-7,8-dihydro-1,8-naphthyridin-4-yl)-1-piperidinecarboxylate (0.024 g, yield; 43%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionTo the residue diluted with dichloromethane (2 mL)
  3. stirringThe mixture was stirred at room temperature for 6 hrs
  4. extractionThe mixture was extracted with ethyl acetate and water
  5. washThe separated organic phase was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by preparative TLC (hexane/ethyl acetate=1/1×2)

Sources & evidence

ORD record
ord-04fc6f108f0b4a43b0cd8141e435efb0
Source dataset
uspto-grants-2003_05
Patent number
US06562811B1

Reaction notes

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