Sodium Thiosulfate → 1-[2-({3-[2-(1-Hydroxycyclobutyl)-1,3-thiazol-5-yl]-5-methylphenyl}amino)pyrimidin-4-yl]ethane-1,2-diol

HRID 410640Notes

Reaction equation

HRID 410640 reaction equation
C([C:3]1C=C[N:6]=[C:5]([NH:9][C:10]2[CH:11]=[C:12]([C:17]3[S:21][C:20]([C:22]4(O)[CH2:25][CH2:24][CH2:23]4)=[N:19][CH:18]=3)[CH:13]=[C:14]([CH3:16])[CH:15]=2)[N:4]=1)=C.C[N+]1([O-])CC[O:31]CC1.[O-]S([O-])(=S)=O.[Na+].[Na+].[CH2:42]1[CH2:46][O:45][CH2:44][CH2:43]1.[OH2:47]>[Os](=O)(=O)(=O)=O>[OH:47][C:22]1([C:20]2[S:21][C:17]([C:12]3[CH:11]=[C:10]([NH:9][C:5]4[N:6]=[C:42]([CH:43]([OH:31])[CH2:44][OH:45])[CH:46]=[CH:3][N:4]=4)[CH:15]=[C:14]([CH3:16])[CH:13]=3)=[CH:18][N:19]=2)[CH2:23][CH2:24][CH2:25]1

Participants

6

Reactant 4

HCID 24477Sodium ThiosulfateHCID 82029Methyl morpholine oxideHCID 21881883Oxolane--water (1/1)HCID 58456376HCID 58456376, compound

Product 1

HCID 584562931-[2-({3-[2-(1-Hydroxycyclobutyl)-1,3-thiazol-5-yl]-5-methylphenyl}amino)pyrimidin-4-yl]ethane-1,2-diol

Reagents, catalysts & solvents 1

HCID 30318Osmium TetroxideCatalyst

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 1-(5-{3-[(4-ethenylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol (200 mg, 0.55 mmol) in THF/water (3.6 mL/1.8 mL) were added osmium tetroxide (4% in water, 0.22 mL, 0.027 mmol) and NMO (77 mg, 0.66 mmol). The reaction mixture was heated to 50° C. overnight. The mixture was cooled to room temperature, treated with aq. Na2S2O3 solution, left to stir overnight, and then extracted with ethyl acetate (3×). The combined organics were washed with brine, dried (sodium sulfate), filtered, concentrated, and purified by column chromatography on silica to afford 1-[2-({3-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-5-methylphenyl}amino)pyrimidin-4-yl]ethane-1,2-diol (47 mg, 0.12 mmol). MS ESI: [M+H]+ m/z 399.1. 1H NMR (500 MHz, DMSO-d6) δ 9.60 (s, 1H), 8.45 (d, J=5.1, 1H), 7.96 (s, 2H), 7.50 (s, 1H), 7.04 (s, 1H), 6.94 (d, J=4.9, 1H), 6.50 (s, 1H), 5.52 (s, 1H), 4.77 (m, 1H), 4.43 (m, 1H), 3.72 (m, 1H), 3.60 (m, 1H), 2.29 (s, 3H), 2.60-1.80 (m, 6H). rhSYK activity=+++

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. waitleft
  3. extractionextracted with ethyl acetate (3×)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by column chromatography on silica

Sources & evidence

ORD record
ord-792ed1a9ad894c2ab7ccdeb4cb99f218
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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