Iodine → 2-(2-Iodo-pyrimidin-4-yl)-4-oxo-1-(2,2,2-trifluoro-ethyl)-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 1968560Notes

Reaction equation

HRID 1968560 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH2:24][C:25]([F:28])([F:27])[F:26])[C:15]([C:17]3[CH:22]=[CH:21][N:20]=[C:19](N)[N:18]=3)=[CH:16][C:10]=2[C:9]1=[O:29])=[O:7])([CH3:4])([CH3:3])[CH3:2].[I-:30].[Cs+].II.N(OCCC(C)C)=O>C(COC)OC.[Cu](I)I>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH2:24][C:25]([F:28])([F:27])[F:26])[C:15]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([I:30])[N:18]=3)=[CH:16][C:10]=2[C:9]1=[O:29])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 807IodineHCID 8053Isoamyl NitriteHCID 24601Cesium iodideHCID 247770392-(2-Amino-pyrimidin-4-yl)-4-oxo-1-(2,2,2-trifluoro-ethyl)-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 866651442-(2-Iodo-pyrimidin-4-yl)-4-oxo-1-(2,2,2-trifluoro-ethyl)-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl esterYield 35%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a well stirred suspension of 2-(2-amino-pyrimidin-4-yl)-4-oxo-1-(2,2,2-trifluoro-ethyl)-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester prepared as reported in Example 9 (180 mg, 0.43 mmol) in dimethoxyethane (10 mL) under N2, cesium iodide (170 mg, 0.65 mmol), bisublimated iodine (83 mg, 0.33 mmol), copper iodide (37 mg, 0.20 mmol) and isopentyl nitrite (0.13 mL, 0.98 mmol) were added in sequence. The reaction mixture was stirred vigorously at 80° C. for 4 hours. After cooling in a ice-water bath, the solid was filtered off. The filtrate was diluted with dichloromethane (100 mL), washed with 30% ammonium hydroxide (50 mL), sodium thiosulphate (50 mL), brine (50 mL), dried over anhydrous Na2SO4 and concentrated. Purification by flash chromatography on silica gel (eluant: dichloromethane/hexane 1/1) afforded 80 mg (35%) of the title compound as solid.

Workup

  1. customprepared
  2. stirringThe reaction mixture was stirred vigorously at 80° C. for 4 hours
  3. temperatureAfter cooling in a ice-water bath
  4. filtrationthe solid was filtered off
  5. additionThe filtrate was diluted with dichloromethane (100 mL)
  6. washwashed with 30% ammonium hydroxide (50 mL), sodium thiosulphate (50 mL), brine (50 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated
  9. customPurification by flash chromatography on silica gel (eluant: dichloromethane/hexane 1/1)

Sources & evidence

ORD record
ord-03350a53bc5f4774a19f57226e95aee9
Source dataset
uspto-grants-2013_04
Patent number
US08426417B2

Reaction notes

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