HCID 59011961, compound → HCID 24829956, compound

HRID 550817Notes

Reaction equation

HRID 550817 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:11]=[C:10]([NH:12][C:13]([N:15]3[CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]3)=[O:14])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1.[Cl:22][C:23]1[CH:24]=[C:25]([Mg]Br)[CH:26]=[CH:27][CH:28]=1>O1CCCC1>[CH3:1][O:2][C:3]1[C:4]2[N:11]=[C:10]([NH:12][C:13]([N:15]3[CH2:20][CH2:19][C:18]([C:27]4[CH:26]=[CH:25][CH:24]=[C:23]([Cl:22])[CH:28]=4)([OH:21])[CH2:17][CH2:16]3)=[O:14])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

4

Reactant 2

HCID 59011961HCID 59011961, compoundHCID 178478127HCID 178478127, compound2×

Product 1

HCID 24829956HCID 24829956, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 4-oxo-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (as prepared in Example 59, 100 mg, 0.33 mmol) in tetrahydrofuran (35 mL) cooled to 0° C. was treated with 3-chlorophenyl magnesium bromide (0.5 M in tetrahydrofuran, 1.6 mL, 0.8 mmol). The resulting mixture was stirred at 25° C. for 3 h. At this time, the reaction mixture was cooled to 0° C. and was treated with an additional amount of 3-chlorophenyl magnesium bromide (0.5 M in tetrahydrofuran, 6 mL, 3.0 mmol). The mixture was then allowed to warm to 25° C. and to stir at 25° C. overnight. At this time, the reaction was quenched with methanol and absorbed onto silica gel (6 g). ISCO chromatography (120 g, Silica, gradient elution 7/93 methanol/methylene chloride) afforded 4-(3-chloro-phenyl)-4-hydroxy-piperidine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (61 mg, 44%) as a light brown solid; LRMS for C18H18ClN5O3S (M+H)+ at m/z=420. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. temperatureAt this time, the reaction mixture was cooled to 0° C.
  2. temperatureto warm to 25° C.
  3. stirringto stir at 25° C. overnight
  4. customAt this time, the reaction was quenched with methanol
  5. customabsorbed onto silica gel (6 g)
  6. washISCO chromatography (120 g, Silica, gradient elution 7/93 methanol/methylene chloride)

Sources & evidence

ORD record
ord-59d513dda6b843ebb26b6172bfcf5fcf
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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