Sodium Sulfite → HCID 57947446, compound

HRID 409826Notes

Reaction equation

HRID 409826 reaction equation
C1C2C(=CC=CC=2)C=C(NC(=O)OC[C@@H](N(C)C(NCC2C=CC=C([F:30])C=2F)=O)CC=C)N=1.C[N+]1([O-])CCOCC1.S([O-])([O-])=O.[Na+].[Na+].[CH:48]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=[C:50]([NH:58][C:59](=[O:82])[O:60][CH2:61][C@@H:62]([N:68]([CH3:81])[C:69]([NH:71][CH2:72][C:73]2[CH:78]=[CH:77][CH:76]=[C:75]([F:79])[C:74]=2Cl)=[O:70])[CH2:63][C@@H:64]([OH:67])[CH2:65][OH:66])[N:49]=1.[CH:83]1[C:92]2[C:87](=[CH:88][CH:89]=[CH:90][CH:91]=2)[CH:86]=[C:85]([NH:93][C:94](=[O:117])[O:95][CH2:96][C@@H:97]([N:103]([CH3:116])[C:104]([NH:106][CH2:107][C:108]2[CH:113]=[CH:112][CH:111]=[C:110]([F:114])[C:109]=2Cl)=[O:105])[CH2:98][C@H:99]([OH:102])[CH2:100][OH:101])[N:84]=1>C1COCC1.O.[Os](=O)(=O)(=O)=O>[CH:48]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=[C:50]([NH:58][C:59](=[O:82])[O:60][CH2:61][C@@H:62]([N:68]([CH3:81])[C:69]([NH:71][CH2:72][C:73]2[CH:78]=[CH:77][CH:76]=[C:75]([F:79])[C:74]=2[F:30])=[O:70])[CH2:63][C@@H:64]([OH:67])[CH2:65][OH:66])[N:49]=1.[CH:83]1[C:92]2[C:87](=[CH:88][CH:89]=[CH:90][CH:91]=2)[CH:86]=[C:85]([NH:93][C:94](=[O:117])[O:95][CH2:96][C@@H:97]([N:103]([CH3:116])[C:104]([NH:106][CH2:107][C:108]2[CH:113]=[CH:112][CH:111]=[C:110]([F:114])[C:109]=2[F:30])=[O:105])[CH2:98][C@H:99]([OH:102])[CH2:100][OH:101])[N:84]=1

Participants

10

Reactant 5

HCID 24437Sodium SulfiteHCID 82029Methyl morpholine oxideHCID 57947408HCID 57947408, compoundHCID 57947515HCID 57947515, compoundHCID 57947912HCID 57947912, compound

Product 2

HCID 57947446HCID 57947446, compoundHCID 57947686HCID 57947686, compound

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-2-(3-(2,3-difluorobenzyl)-1-methylureido)pent-4-enyl isoquinolin-3-ylcarbamate (3.42 g, 7.52 mmol) in THF (100 mL) and water (25.0 mL) were added 4-methylmorpholine N-oxide (4.4 g, 37.6 mmol) and osmium tetroxide (254.2 mg, 0.75 mmol). The resulting solution was stirred overnight. To this mixture was added sodium sulfite (3 g) and the mixture was stirred for 2 h. The solid was then removed by filtration. The filtrate was diluted with ethyl acetate (200 mL). The organic layer was washed with HCl (0.5 N), saturated NaHCO3, and brine, filtered, and partially concentrated. The mixture was filtered and the solid was collected and dried to give a mixture of (2S,4R)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4,5-dihydroxypentyl isoquinolin-3-ylcarbamate and (2S,4S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4,5-dihydroxypentyl isoquinolin-3-ylcarbamate (1 g) as 1:2 ratio. The filtrate was concentrated and purified by RP-HPLC using a mixture of acetonitrile and water to give (2S,4R)-2-(3-(2,3-difluorobenzyl)-1-methylureido)-4,5-dihydroxypentyl isoquinolin-3-ylcarbamate (14 mg), (2S,4S)-2-(3-(2,3-difluorobenzyl)-1-methylureido)-4,5-dihydroxypentyl isoquinolin-3-ylcarbamate (10 mg), and a mixture of both (300 mg). LRMS (M+H+) m/z 489.2.

Workup

  1. stirringthe mixture was stirred for 2 h
  2. customThe solid was then removed by filtration
  3. additionThe filtrate was diluted with ethyl acetate (200 mL)
  4. washThe organic layer was washed with HCl (0.5 N), saturated NaHCO3, and brine
  5. filtrationfiltered
  6. concentrationpartially concentrated
  7. filtrationThe mixture was filtered
  8. customthe solid was collected
  9. customdried
  10. customto give
  11. concentrationThe filtrate was concentrated
  12. custompurified by RP-HPLC
  13. additiona mixture of acetonitrile and water

Sources & evidence

ORD record
ord-e85387a43d3e4c54bf293bf821efd360
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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