Tetrahydrofuran → HCID 58094904, compound

HRID 1530119Notes

Reaction equation

HRID 1530119 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH:10]=C)=[CH:6][N:5]2[C:12]=1[C:13]1[S:14][C:15]([C:24]2[N:28]=[CH:27][N:26]([CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][O:30]3)[N:25]=2)=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:17]=1.[O:35]1CCCC1.I([O-])(=O)(=O)=O.[Na+]>O.[Os](=O)(=O)(=O)=O>[CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH:10]=[O:35])=[CH:6][N:5]2[C:12]=1[C:13]1[S:14][C:15]([C:24]2[N:28]=[CH:27][N:26]([CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][O:30]3)[N:25]=2)=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:17]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 23667635Sodium periodateHCID 58094807HCID 58094807, compound

Product 1

HCID 58094904HCID 58094904, compoundYield 34.1%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent3×

Procedure

To the solution of 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}-6-vinylimidazo[1,2-a]pyridine (0.747 g, 1.59 mmol) in Tetrahydrofuran (55 mL, 680 mmol) and Water (16 mL, 890 mmol) was added Sodium metaperiodate (0.852 g, 3.98 mmol), followed by 0.157 M of Osmium tetraoxide in Water (0.53 mL, 0.083 mmol). The solution was stirred at r.t, for 3 days. The mixture was diluted with ˜100 mL of water, filtered to collect the solid product as the first crop of 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}imidazo[1,2-a]pyridine-6-carbaldehyde (0.255 g, 24% yield). LCMS: (FA) ES+ 471. 1H NMR (400 MHz, d1-chloroform) δ 10.56 (σ, 1H), 10.00 (σ, 1H), 8.30 (σ, 1H), 7.94-7.97 (m, 2H), 7.82-7.85 (m, 1H), 7.69-7.71 (m, 1H), 7.46 (m, 3H), 5.48-5.51 (dd, J=8.78, 2.76 Hz, 1H), 4.06-4.09 (m, 1H), 3.73-3.77 (m, 1H), 2.85 (s, 3H), 2.02-2.15 (m, 3H), 1.59-1.69 (m, 3H). The filtrate was rotavaped to remove THF, extracted with 5% MeOH/DCM (4×60 mL). The combined DCM solution was dried over Na2SO4, filtered, rotavaped to give a crude material. Chromatograph in a 40 g ISCO column using MeOH/DCM (0/100 to 5/95) gave the second crop of 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}imidazo[1,2-a]pyridine-6-carbaldehyde (fast fraction, 0.104 g, 14% yield), and 1-(2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}imidazo[1,2-a]pyridin-6-yl)ethane-1,2-diol (slow fraction, 0.243 g, 30.3% yield). LCMS: (FA) ES+ 503. 1H NMR (400 MHz, d1-chloroform & d4-methanol) δ 9.90 (σ, 1H), 8.28 (σ, 1H), 7.86-7.88 (m, 2H), 7.54-7.57 (d, J=9.29 Hz, 1H), 7.37-7.41 (m, 4H), 5.44-5.47 (m, 1H), 4.80-4.82 (m, 1H), 4.02-4.05 (m, 1H), 3.68-3.80 (m, 3H), 2.73 (s, 3H), 2.00-2.11 (m, 3H), 1.65-1.68 (m, 3H).

Workup

  1. filtrationfiltered

Sources & evidence

ORD record
ord-461f4a5c01134feabf0e80569b7140c8
Source dataset
uspto-grants-2015_07
Patent number
US09090601B2

Reaction notes

Loading…