Pyridine → HCID 68007819, compound

HRID 527043Notes

Reaction equation

HRID 527043 reaction equation
C(C1(O)C[CH2:8][CH2:7][C@H:6]([NH:10][C:11]2[C:16]([F:17])=[CH:15][N:14]=[C:13]([C:18]3[C:26]4[C:21](=[N:22][CH:23]=[C:24]([Cl:27])[CH:25]=4)[N:20]([S:28]([C:31]4[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=4)(=[O:30])=[O:29])[CH:19]=3)[N:12]=2)C1)C=C.N1C=CC=CC=1.C[N+]1([O-])[CH2:51][CH2:50][O:49]CC1.S(=O)(O)[O-:54].[Na+].[CH3:58][C:59]([OH:62])([CH3:61])[CH3:60]>C1COCC1.O.[Os](=O)(=O)(=O)=O>[Cl:27][C:24]1[CH:25]=[C:26]2[C:18]([C:13]3[N:12]=[C:11]([NH:10][C@H:6]4[CH2:7][CH2:8][CH2:60][C@@:59]([CH2:61][CH:51]([OH:54])[CH2:50][OH:49])([OH:62])[CH2:58]4)[C:16]([F:17])=[CH:15][N:14]=3)=[CH:19][N:20]([S:28]([C:31]3[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=3)(=[O:29])=[O:30])[C:21]2=[N:22][CH:23]=1

Participants

9

Reactant 5

HCID 1049PyridineHCID 6386tert-ButanolHCID 82029Methyl morpholine oxideHCID 23665763Sodium BisulfiteHCID 68007995HCID 68007995, compound

Product 1

HCID 68007819HCID 68007819, compound

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (3S)-1-allyl-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]cyclohexanol, 58c, (0.30 g, 0.54 mmol) in 2-methyl-2-propanol (9.23 mL), THF (3.69 mL) and water (1.85 mL) was added pyridine (0.09 mL, 1.08 mmol) and osmium tetroxide (0.27 mL of 2.5% w/v, 0.03 mmol) and 4-methylmorpholine N-oxide (0.07 mL, 0.65 mmol). The reaction mixture was heated to 80° C. for 20 hours. After cooling to room temperature, the mixture was diluted into aqueous saturated sodium bisulfite solution and extracted twice with 20% isopropanol/CH2Cl2. The combined organic phases were washed with more aqueous saturated sodium bisulfite solution, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography using 5-10% MeOH/CH2Cl2 gradient to afford 175 mg of the desired product as a racemic mixture, 58d.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted twice with 20% isopropanol/CH2Cl2
  3. washThe combined organic phases were washed with more aqueous saturated sodium bisulfite solution
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-348c925ea02746f2805a24adc50b63a5
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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