Acetonitrile → HCID 86717476, compound

HRID 712018Notes

Reaction equation

HRID 712018 reaction equation
[CH:1]([NH:4]C(C)C)(C)[CH3:2].C([Li])CCC.C(#N)C.[N+:16]([C:19]1[C:20]([NH:28][CH:29]2[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]2)=[C:21]2[S:27][CH:26]=[CH:25][C:22]2=[N:23][CH:24]=1)([O-:18])=[O:17]>O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O>[OH:35][C:32]1([CH2:2][C:1]#[N:4])[CH2:31][CH2:30][CH:29]([NH:28][C:20]2[C:19]([N+:16]([O-:18])=[O:17])=[CH:24][N:23]=[C:22]3[CH:25]=[CH:26][S:27][C:21]=23)[CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 7912DiisopropylamineHCID 86717475HCID 86717475, compoundHCID 178418339Butyllithium

Product 1

HCID 86717476HCID 86717476, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N,N-diisopropylamine (0.19 mL, 1.4 mmol) in tetrahydrofuran (3 mL) was cooled to 0° C. 1.6 M n-butyllithium in hexanes (0.86 mL, 1.4 mmol) was added dropwise, keeping the temperature below 5° C. After the addition was complete, the mixture was stirred for 20 min at 0° C. The mixture was then cooled to −78° C. and acetonitrile (0.072 mL, 1.4 mmol) was added, keeping the temperature below −70° C. After the addition was complete, the mixture was stirred for 20 min at −78° C. and a mixture of 4-[(6-nitrothieno[3,2-b]pyridin-7-yl)amino]cyclohexanone (0.20 g, 0.69 mmol) in tetrahydrofuran (3 mL)/hexamethylphosphoramide (3 mL) was added, keeping the temperature below −70° C. After the addition was complete, the mixture was stirred for 30 min at −78° C. and then stirred at room temperature for 5 h. The mixture was partitioned between methylene chloride and sat. aq. NH4Cl solution. The organic phase was washed with water, dried over sodium sulfate, concentrated and purified on silica gel column (eluting with 0-30% EtOAc in methylene chloride) to give the desired product (0.11 g, 48%). LCMS calculated for C15H17N4O3S (M+H)+: m/z=333.1. Found: 333.0.

Workup

  1. customthe temperature below 5° C
  2. additionAfter the addition
  3. temperatureThe mixture was then cooled to −78° C.
  4. customthe temperature below −70° C
  5. additionAfter the addition
  6. stirringthe mixture was stirred for 20 min at −78° C.
  7. additionwas added
  8. customthe temperature below −70° C
  9. additionAfter the addition
  10. stirringthe mixture was stirred for 30 min at −78° C.
  11. stirringstirred at room temperature for 5 h
  12. customThe mixture was partitioned between methylene chloride and sat. aq. NH4Cl solution
  13. washThe organic phase was washed with water
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated
  16. custompurified on silica gel column (eluting with 0-30% EtOAc in methylene chloride)

Sources & evidence

ORD record
ord-14dc6c28809f4b8db9fb0aa1baa8ccd9
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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