Sodium periodate → HCID 66860172, compound

HRID 1803306Notes

Reaction equation

HRID 1803306 reaction equation
I([O-])(=O)(=O)=[O:2].[Na+].[F:7][C:8]([F:13])([F:12])[C:9]([OH:11])=[O:10].[Cl:14][C:15]1[N:16]=[CH:17][N:18]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:27]3[N:44]=[C:30]4[CH:31]([C:37]5[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=5)[CH2:32][C:33](=C)[CH2:34][CH2:35][N:29]4[N:28]=3)=[CH:22][C:21]=2[O:45][CH3:46])[CH:19]=1>O.C1COCC1.[Cl-].[Na+].O.[Os](=O)(=O)(=O)=O>[F:7][C:8]([F:13])([F:12])[C:9]([OH:11])=[O:10].[Cl:14][C:15]1[N:16]=[CH:17][N:18]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:27]3[N:44]=[C:30]4[CH:31]([C:37]5[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=5)[CH2:32][C:33](=[O:2])[CH2:34][CH2:35][N:29]4[N:28]=3)=[CH:22][C:21]=2[O:45][CH3:46])[CH:19]=1

Participants

7

Reactant 2

HCID 23667635Sodium periodateHCID 66859881HCID 66859881, compound

Product 1

HCID 66860172HCID 66860172, compoundYield 48%

Reagents, catalysts & solvents 4

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of sodium periodate (138 mg, 0.645 mmol) in water (5.0 mL) was added over a 10 min period, via pipet, to a vigorously stirred solution of the N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-9-(4-fluorophenyl)-7-methylene-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amine (100 mg, 0.215 mmol, from example 133) and osmium tetroxide (5.47 mg, 0.022 mmol) in THF (5.0 mL). The reaction was stirred for 1 h and then diluted with water (150 mL)/brine (100 mL) and extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude product was purified using reverse phase preparatory HPLC (MeOH/water/trifluoroacetic acid) to afford the titled compound as the TFA salt (60 mg, 47% yield). LC-MS (M+H)+ 467.1. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 9.24 (1 H, br. s.), 8.12 (1 H, d, J=1.5 Hz), 7.33 (1 H, d, J=2.1 Hz), 7.19-7.24 (1 H, m), 7.07-7.18 (5 H, m), 4.71 (1H, dd, J=8.5, 4.0 Hz), 4.54-4.64 (1 H, m), 4.45-4.54 (1 H, m), 3.90 (3 H, s), 3.44 (1 H, dd, J=14.3, 8.5 Hz), 3.16 (1 H, dd, J=14.3, 4.0 Hz), 2.89-3.06 (2 H, m).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified

Sources & evidence

ORD record
ord-a8a423bd16f0465eb39660f66ae23ce0
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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