Dimethylformamide → HCID 57963110, compound

HRID 1775155Notes

Reaction equation

HRID 1775155 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 (26, 2.90 g, 6.74 mmol) in 25.0 mL of tetrahydrofuran at −35° C. under an atmosphere of 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 (27, 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-c8405f4251b94c6ca4477aaecb4d8001
Source dataset
uspto-grants-2016_02
Patent number
US09260437B2

Reaction notes

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