Dimethylformamide → HCID 57963110, compound

HRID 509949Notes

Reaction equation

HRID 509949 reaction equation
[C:1]([O:5][C:6](=[O:26])[N:7]([C:18]1[CH:23]=[CH:22][C:21](Br)=[C:20]([F:25])[N:19]=1)[CH2:8][C:9]1[CH:10]=[N:11][C:12]([O:16][CH3:17])=[C:13]([F:15])[CH:14]=1)([CH3:4])([CH3:3])[CH3:2].C([Mg]Cl)(C)C.CN(C)[CH:34]=[O:35].[Cl-].[NH4+]>O1CCCC1>[C:1]([O:5][C:6](=[O:26])[N:7]([C:18]1[CH:23]=[CH:22][C:21]([CH:34]=[O:35])=[C:20]([F:25])[N:19]=1)[CH2:8][C:9]1[CH:10]=[N:11][C:12]([O:16][CH3:17])=[C:13]([F:15])[CH:14]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 57963058HCID 57963058, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 57963110HCID 57963110, compoundYield 70.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-45 °C

Procedure

To (5-bromo-6-fluoro-pyridin-2-yl)-(5-fluoro-6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (60, 2.90 g, 6.74 mmol) in 25.0 mL of tetrahydrofuran at −35° C. under nitrogen, isopropylmagnesium chloride (3.54 mL, 2.00 M in tetrahydrofuran, 7.08 mmol) was added and the reaction was allowed to come to 0° C. over an hour. The reaction was cooled to −45° C. and N,N-dimethylformamide (1.0 mL, 13.0 mmol) was added. The reaction was allowed to warm to room temperature over 2 hours, then poured into aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 20% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (61, 1.80 g).

Workup

  1. waitto come to 0° C. over an hour
  2. temperatureto warm to room temperature over 2 hours
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe resulting material was purified by silica gel column chromatography
  8. washeluting with 20% ethyl acetate in hexane
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-6e7003c0b5804a85b4218c859669cf2a
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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