Water → Methyl (4-{3-cyano-4-(1,2-dihydroxyethyl)-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate

HRID 2401826Notes

Reaction equation

HRID 2401826 reaction equation
[C:1]([C:3]1[C:7]([CH:8]=[CH2:9])=[C:6]([C:10]2[N:14]=[CH:13][N:12]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[N:11]=2)[S:5][C:4]=1[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28](=[O:31])[O:29][CH3:30])[CH:22]=1)#[N:2].C[N+]1([O-])CC[O:36]CC1.[OH2:40]>C(O)(C)(C)C.CC(C)=O.C(Cl)Cl.CO.[Os](=O)(=O)(=O)=O.O>[C:1]([C:3]1[C:7]([CH:8]([OH:36])[CH2:9][OH:40])=[C:6]([C:10]2[N:14]=[CH:13][N:12]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[N:11]=2)[S:5][C:4]=1[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28](=[O:31])[O:29][CH3:30])[CH:22]=1)#[N:2]

Participants

9

Reactant 3

HCID 962WaterHCID 82029Methyl morpholine oxide2×HCID 68100370methyl (4-{3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-4-vinyl-2-thienyl}pyridin-2-yl)carbamate

Product 1

HCID 68100371Methyl (4-{3-cyano-4-(1,2-dihydroxyethyl)-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamateYield 57.6%

Reagents, catalysts & solvents 5

HCID 962WaterCatalystHCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 6386tert-ButanolSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To the suspension of methyl (4-{3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-4-vinyl-2-thienyl}pyridin-2-yl)carbamate (0.625 g, 1.34 mmol) in tert-butyl alcohol (3.0 mL) and acetone (30 mL) was added N-methylmorpholine N-oxide (0.315 g, 2.69 mmol), followed by water (1.0 mL) then 0.157 M of osmium tetraoxide in Water (0.257 mL, 0.0404 mmol). The pale yellow suspension was stirred at room temperature for 17 hours. N-Methylmorpholine N-oxide (0.315 g, 2.69 mmol) was added and the suspension was stirred for 3 more hours, then heated to reflux for 7 hours. The mixture was cooled to room temperature, rotavaped and azeotroped with MeOH to give a solid crude residue. The crude solid was partially dissolved in DCM-MeOH, coated on silica gel, evaporated in rotavapor and chromatographed in a silica gel column using an elution of MeOH/DCM (0/100 to 5/95) to afford a solid product (0.365 g, yield 57.6%). LC/MS: (FA) ES+ 471; ES− 469. 1H NMR (400 MHz, d-chloroform/d4-methanol) δ 8.35 (m, 2H), 8.30 (m, 1H), 7.40 (m, 1H), 5.47-5.49 (m, 1H), 5.31-5.33 (m, 1H), 4.03-4.07 (m, 1H), 3.87 (m, 1H), 3.79 (s, 3H), 3.71-3.81 (m, 2H), 2.13 (m, 1H), 2.00-2.02 (m, 2H), 1.65-1.70 (m, 3H).

Workup

  1. stirringthe suspension was stirred for 3 more hours
  2. temperatureheated
  3. temperatureto reflux for 7 hours
  4. temperatureThe mixture was cooled to room temperature
  5. customazeotroped with MeOH
  6. customto give a solid crude residue
  7. customevaporated in rotavapor
  8. customchromatographed in a silica gel column
  9. washan elution of MeOH/DCM (0/100 to 5/95)

Sources & evidence

ORD record
ord-64d01cf8de064980943053eb5cc1d36a
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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