Benzyl (2,4-difluoro-3-formylphenyl)carbamate → HCID 58316916, compound

HRID 1187287Notes

Reaction equation

HRID 1187287 reaction equation
[Cl:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([S:12]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:4]=2[N:5]=[CH:6][N:7]=1.C([Mg]Cl)(C)C.[CH2:27]([O:34][C:35](=[O:47])[NH:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([CH:44]=[O:45])[C:38]=1[F:46])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C1(C)C=CC=CC=1[Mg]Cl>O1CCCC1>[CH2:27]([O:34][C:35](=[O:47])[NH:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([CH:44]([C:10]2[C:3]3[C:2]([Cl:1])=[N:7][CH:6]=[N:5][C:4]=3[N:8]([S:12]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[CH:9]=2)[OH:45])[C:38]=1[F:46])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 58086235Benzyl (2,4-difluoro-3-formylphenyl)carbamateHCID 58316898HCID 58316898, compound2×HCID 178418918HCID 178418918, compoundHCID 178424304HCID 178424304, compound

Product 1

HCID 58316916HCID 58316916, compoundYield 26.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-50 °C

Procedure

In a round bottom flask, 4-chloro-5-iodo-7-(toluene-4-sulfonyl)-7H-pyrrolo[2,3-d]pyrimidine (29, 1.549 g, 3.572 mmol) is combined with 25.0 mL of tetrahydrofuran and the solution is cooled to −50° C. under nitrogen. Isopropylmagnesium chloride (2.76 mL, 2.0 M in tetrahydrofuran, 5.00 mmol) is added slowly and the reaction is allowed to warm to 5° C. over 70 minutes, then cooled to −45° C. In a separate vessel, (2,4-difluoro-3-formyl-phenyl)-carbamic acid benzyl ester (33, 805 mg, 2.76 mmol) in 5 mL of tetrhydrofuran is cooled to −5° C. and o-tolylmagnesium chloride (2.76 mL, 1 M in tetrahydrofuran, 2.76 mmol) is added dropwise slowly, maintaining the temperature at −5° C. for 1 hour. This is then cooled to −30° C. and added to the above 4-chloro-5-iodo-7-(toluene-4-sulfonyl)-7H-pyrrolo[2,3-d]pyrimidine reaction mixture. The resulting reaction mixture is warmed to room temperature over 2-3 hours, then quenched with the addition of 1 M aqueous citric acid and extracted with ethyl acetate. The organic layer is washed with water, brine and dried over magnesium sulfate, then filtered and the filtrate is concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (34, 445 mg). MS (ESI) [M+H+]+=598.8.

Workup

  1. temperatureto warm to 5° C. over 70 minutes
  2. temperaturecooled to −45° C
  3. temperaturemaintaining the temperature at −5° C. for 1 hour
  4. temperatureThis is then cooled to −30° C.
  5. customThe resulting reaction mixture
  6. temperatureis warmed to room temperature over 2-3 hours
  7. customquenched with the addition of 1 M aqueous citric acid
  8. extractionextracted with ethyl acetate
  9. washThe organic layer is washed with water, brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationthe filtrate is concentrated under vacuum
  13. customThe resulting material is purified by silica gel column chromatography
  14. washeluting with ethyl acetate and hexane
  15. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-24fc91a7d031446b812e53b10b63dc40
Source dataset
uspto-grants-2014_03
Patent number
US08673928B2

Reaction notes

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