Water → Racemic 1-{4-[5-(2-isopropylamino-6-methyl-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-ethane-1,2-diol

HRID 2069462Notes

Reaction equation

HRID 2069462 reaction equation
[CH:1]([NH:4][C:5]1[N:10]=[C:9]([CH3:11])[CH:8]=[C:7]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]=[CH2:24])=[CH:19][CH:18]=3)[N:13]=2)[N:6]=1)([CH3:3])[CH3:2].[OH2:25].[OH2:26].C[N+]1([O-])CCOCC1>CC(C)=O.C(Cl)Cl.O=[Os](=O)(=O)=O>[CH:1]([NH:4][C:5]1[N:6]=[C:7]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][C:20]([CH:23]([OH:26])[CH2:24][OH:25])=[CH:21][CH:22]=3)[N:13]=2)[CH:8]=[C:9]([CH3:11])[N:10]=1)([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 962WaterHCID 2724197N-Methylmorpholine N-oxide monohydrateHCID 68509545Isopropyl-{4-methyl-6-[3-(4-vinyl-phenyl)-[1,2,4]oxadiazol-5-yl]-pyrimidin-2-yl}-amine2×

Product 1

HCID 68508784Racemic 1-{4-[5-(2-isopropylamino-6-methyl-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-ethane-1,2-diol

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalyst2×HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of isopropyl-{4-methyl-6-[3-(4-vinyl-phenyl)-[1,2,4]oxadiazol-5-yl]-pyrimidin-2-yl}-amine (Intermediate 8: 2.78 g, 8.67 mmol) in acetone (45 mL) are added water (4 mL) and a 2.5% aq. solution of OsO4 (136 μL), followed by N-methyl-morpholine-N-oxide monohydrate (1.4 g, 10.4 mmol). The reaction mixture is stirred at rt for 18 h. Another 68 μL of 2.5% aq. solution of OsO4 is added and stirring is continued for another 3 h. The mixture is then diluted with DCM (150 mL), and washed with water (3×50 mL), dried over MgSO4, filtered and evaporated to give 0.97 g of racemic 1-{4-[5-(2-isopropylamino-6-methyl-pyrimidin-4-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-ethane-1,2-diol as a brown solid; LC-MS: tR=0.84 min; [M+H]+=356.04. 1H NMR (CDCl3) δ 1.30 (d, J=6.5 Hz, 6H), 2.16 (s br, 1H), 2.49 (s, 3H), 2.74 (s br, 1H), 3.72 (dd, J=11.0, 8.0 Hz, 1H), 3.86 (dd, J=11.0, 3.3 Hz, 0H), 4.31 (m, 1H), 4.94 (dd, J=7.8, 3.3 Hz, 1H), 5.28 (s br, 1H), 7.30 (s, 1H), 7.55 (d, J=8.3 Hz, 2H), 8.20 (d, J=8.3 Hz, 2H).

Workup

  1. stirringstirring
  2. waitis continued for another 3 h
  3. washwashed with water (3×50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-edce208a6b7f4a9f92c953da2b98696a
Source dataset
uspto-grants-2012_10
Patent number
US08299086B2

Reaction notes

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