Dimethylacetamide → HCID 58381980, compound

HRID 1628023Notes

Reaction equation

HRID 1628023 reaction equation
Br[C:2]1[N:3]=[C:4]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]2=[N:6][CH:7]=1.BrC1C(N)=NC=C(Br)N=1.C(C1C=C[C:41]([O:44]C)=[CH:40]C=1)#C.[Li]CCCC.CC(N(C)C)=O>C1COCC1.O.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O.CC(O)=O>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]3=[N:6][CH:7]=[C:2]([C:41](=[O:44])[CH3:40])[N:3]=[C:4]3[CH:10]=2)=[CH:12][CH:13]=1

Participants

11

Reactant 5

HCID 31374DimethylacetamideHCID 2510201-Ethynyl-4-methoxybenzeneHCID 6200042-Amino-3,5-dibromopyrazineHCID 58382232HCID 58382232, compoundHCID 178418339Butyllithium

Product 1

HCID 58381980HCID 58381980, compoundYield 76%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
-75 °C

Procedure

2-Bromo-6-(4-methoxyphenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (1.5 g, 3.5 mmol, prepared using A from 3,5-dibromopyrazin-2-amine with 1-ethynyl-4-methoxybenzene, B and C) in THF (20 mL) was cooled to about −75° C. then n-BuLi (1.44 mL, 3.45 mmol) was added dropwise keeping the temperature below −70° C. After about 5 min DMA (1.30 mL, 13.8 mmol) was added keeping the temperature below about −65° C. The mixture was stirred for about 30 min at about −75° C. then allowed to warm slowly to about 0° C. AcOH (˜0.5 mL) was added then the mixture was diluted with water (40 mL), saturated aqueous Na2CO3 (20 mL) and EtOAc (40 mL). The layers were separated then the organic layer was washed with brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The material was purified by flash chromatography on an 80 g silica column with 85:15 DCM/EtOAc as an eluent to give 1-(6-(4-methoxyphenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)ethanone (1.04 g, 76%): LC/MS (Table 2, Method a) Rt=3.42 min; MS m/z 398 (M+H)+.

Workup

  1. customthe temperature below −70° C
  2. customthe temperature below about −65° C
  3. temperatureto warm slowly to about 0° C
  4. customThe layers were separated
  5. washthe organic layer was washed with brine (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe material was purified by flash chromatography on an 80 g silica column with 85:15 DCM/EtOAc as an eluent

Sources & evidence

ORD record
ord-80d061917adb43b5aa3420fce168a6d7
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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