Benzaldehyde → HCID 57635346, compound

HRID 535951Notes

Reaction equation

HRID 535951 reaction equation
Br[C:2]1[N:6]2[CH2:7][CH2:8][N:9]([CH3:11])[CH2:10][C:5]2=[C:4]([C:12]([NH:14][C@@H:15]([C:20]([CH3:23])([CH3:22])[CH3:21])[C:16]([NH:18][CH3:19])=[O:17])=[O:13])[N:3]=1.CC(C)(C)[C@H](NC(C1N=C(C#CC2C=CC=CC=2)N2CCN(C)CC=12)=O)C(NC)=O.C[Si](Cl)(C)C.C([Mg]Cl)(C)C.[CH:64](=[O:71])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1>C1COCC1>[CH3:21][C:20]([CH3:23])([CH3:22])[C@H:15]([NH:14][C:12]([C:4]1[N:3]=[C:2]([CH:64]([OH:71])[C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[N:6]2[CH2:7][CH2:8][N:9]([CH3:11])[CH2:10][C:5]=12)=[O:13])[C:16]([NH:18][CH3:19])=[O:17]

Participants

7

Reactant 5

HCID 240BenzaldehydeHCID 6397ChlorotrimethylsilaneHCID 57635127HCID 57635127, compoundHCID 57635398HCID 57635398, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 57635346HCID 57635346, compoundYield 18.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under a nitrogen atmosphere (S)-3-bromo-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-7-methyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide (Compound 203) (0.050 g, 0.13 mmol) was dissolved in THF and trimethysilylchloride (0.045 g, 0.41 mmol) was added. The resulting solution was stirred for 3 hours. Isopropylmagnesium chloride solution (2M in THF, 0.27 mL, 0.54 mmol) was added dropwise at 0° C. and the mixture was stirred for 15 minutes, then benzaldehyde (0.028 g, 0.26 mmol) was added at 0° C. and the resulting mixture was stirred cold for 40 minutes. The mixture was quenched at 0° C. with NH4Cl saturated solution, stirred for 10 min and concentrated. The reaction mixture was then extracted repeatedly with 20% i-PrOH/DCM and the combined organic extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by prep LC/MS using 5-95% gradient acetonitrile/water with 0.1% formic acid. The resulting material was filtered through Strata SCX SPE tube to give (0.010 g, 18%) of Compound 295 as a free base. 1H-NMR (400 MHz, CD3OD) δ: 1.05 (s, 9H), 2.43 (s, 3H), 2.75 (m, 5H), 3.69 (m, 1H), 3.88 (m, 2H), 4.09 (m, 1H), 4.32 (s, 1H), 7.53 (t, 2H), 5.97 (m 1H), 7.29 (m, 1H), 7.38 (m, 4H); LCMS (+ESI) m/z 414.2 [M+H]+.

Workup

  1. stirringthe mixture was stirred for 15 minutes
  2. stirringthe resulting mixture was stirred cold for 40 minutes
  3. customThe mixture was quenched at 0° C. with NH4Cl saturated solution
  4. stirringstirred for 10 min
  5. concentrationconcentrated
  6. extractionThe reaction mixture was then extracted repeatedly with 20% i-PrOH/DCM
  7. dry with materialthe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by prep LC/MS
  11. filtrationThe resulting material was filtered through Strata SCX SPE tube

Sources & evidence

ORD record
ord-b88d1ca575524e8287655ce4e485e2ab
Source dataset
uspto-grants-2014_10
Patent number
US08859538B2

Reaction notes

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