Dimethylformamide → HCID 178480269, compound

HRID 2064502Notes

Reaction equation

HRID 2064502 reaction equation
C([Mg]Br)(C)C.C([Li])CCC.[C:11]([C:15]1[N:19]([CH3:20])[N:18]([CH2:21][CH:22]2[CH2:24][CH2:23]2)/[C:17](=[N:25]/[C:26](=[O:38])[C:27]2[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=2F)/[CH:16]=1)([CH3:14])([CH3:13])[CH3:12].CN([CH:42]=[O:43])C>C1COCC1.C(N(CC)CC)C.CO.C(OCC)(=O)C>[C:11]([C:15]1[N:19]([CH3:20])[N:18]([CH2:21][CH:22]2[CH2:24][CH2:23]2)/[C:17](=[N:25]/[C:26](=[O:38])[C:27]2[CH:32]=[C:31]([C:33]([F:34])([F:36])[F:35])[CH:30]=[CH:29][C:28]=2[CH:42]=[O:43])/[CH:16]=1)([CH3:13])([CH3:14])[CH3:12]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 178418339ButyllithiumHCID 178418365HCID 178418365, compoundHCID 178480270HCID 178480270, compound

Product 1

HCID 178480269HCID 178480269, compoundYield 93%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To the solution of isopropylmagnesium bromide (3 mL, 2.97 mmol, 1.0 M solution in THF) was added n-butyllithium (2.4 ml, 5.93 mmol, 2.5 M solution in hexane). The mixture was cooled to −78° C., and then a solution of Example 9G (0.680 g, 1.48 mmol) in THF (2 mL) was added dropwise. The mixture was stirred for 1 hour at −78° C. then DMF (0.460 mL, 5.93 mmol) was added, and the mixture was allowed to warm to room temperature. The mixture was quenched with saturated aqueous NH4Cl and extracted with ethyl acetate. The organic layer was washed with brine and concentrated under reduced pressure. Purification of the residue by chromatography (silica gel, eluted with a gradient of 5-50% hexanes in solvent B, solvent B: 10:1:0.5 ethyl acetate:methanol:triethylamine) afforded the title compound (560 mg, 1.374 mmol, 93% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.42-0.52 (m, 4H), 1.24-1.36 (m, 1H), 1.42 (s, 9H), 3.98 (s, 3H), 4.30 (d, J=7.14 Hz, 2H), 6.92 (s, 1H), 7.33-7.43 (m, 1H), 7.70-7.78 (m, 1H), 8.7 (dd, J=6.74, 2.38 Hz, 1H), 10.58 (s, 1 H); MS (ESI) m/z 408 [M+H]+, 406[M−H]−.

Workup

  1. temperatureto warm to room temperature
  2. customThe mixture was quenched with saturated aqueous NH4Cl
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue by chromatography (silica gel
  7. washeluted with a gradient of 5-50% hexanes in solvent B, solvent B

Sources & evidence

ORD record
ord-cd76648747f24408bffcf6a4cabad248
Source dataset
uspto-grants-2012_10
Patent number
US08288428B2

Reaction notes

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