Diisopropylethylamine → HCID 71087789, compound

HRID 927756Notes

Reaction equation

HRID 927756 reaction equation
[CH3:1][C:2]([CH3:14])([O:4][C:5]([NH:7][C:8]([CH3:13])([C:10](O)=[O:11])[CH3:9])=[O:6])[CH3:3].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.O.S(O)(O)(=O)=O.O[NH:64][C:65]([NH2:67])=[NH:66]>CN(C=O)C>[C:2]([O:4][C:5](=[O:6])[NH:7][C:8]([C:10]1[O:11][N:66]=[C:65]([NH2:67])[N:64]=1)([CH3:13])[CH3:9])([CH3:14])([CH3:3])[CH3:1]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 2724699PyBOPHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 178513205HCID 178513205, compound

Product 1

HCID 71087789HCID 71087789, compoundYield 8.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a colorless solution of N-[(1,1-dimethylethoxy)carbonyl]-2-methyl-alanine (CAN 30992-29-1; 1.0 g, 4.92 mmol) in DMF (24 mL) was added (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (3.07 g, 5.9 mmol) and DIEA (1.72 mL, 4.9 mmol), and the resulting pale yellow solution was stirred under argon for 30 minutes at room temperature. This mixture was added dropwise over 40 minutes to a suspension of hydroxyguanidine sulfate monohydrate (3.93 g, 14.8 mmol), DIEA (2.6 mL, 7.4 mmol), and molecular sieves (4 Å, 2 g) in DMF (35 mL) under argon, the temperature not exceeding 25° C. Once addition was complete another 2 g of molecular sieves was added and the reaction mixture (pale yellow suspension) was stirred for 1.5 hours under argon at room temperature then stirred at 130° C. for 20 hours. After cooling to room temperature the mixture was filtered through Celite®. The filtrate was concentrated in vacuo (HV pump) and the residue was stirred vigorously with 2-methoxy-2-methylpropane (40 mL) and 1N NaOH (40 mL) for 20 h. Phases were separated; the aqueous phase was washed with 2-methoxy-2-methylpropane (2×10 mL). Combined organic extracts were washed with water, then dried with Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography (silica gel, 50 g, 0% to 100% EtOAc in hexanes) to give the title compound (106 mg, 8.9%), which was used without further purification.

Workup

  1. customexceeding 25° C
  2. additionOnce addition
  3. additionwas added
  4. stirringthe reaction mixture (pale yellow suspension) was stirred for 1.5 hours under argon at room temperature
  5. stirringthen stirred at 130° C. for 20 hours
  6. temperatureAfter cooling to room temperature the mixture
  7. filtrationwas filtered through Celite®
  8. concentrationThe filtrate was concentrated in vacuo (HV pump)
  9. stirringthe residue was stirred vigorously with 2-methoxy-2-methylpropane (40 mL) and 1N NaOH (40 mL) for 20 h
  10. customPhases were separated
  11. washthe aqueous phase was washed with 2-methoxy-2-methylpropane (2×10 mL)
  12. washCombined organic extracts were washed with water
  13. dry with materialdried with Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customThe residue was purified by chromatography (silica gel, 50 g, 0% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-135fca3af5924526b8714507bc302be4
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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