4-Cyanobenzoyl chloride → HCID 67774340, compound

HRID 1808859Notes

Reaction equation

HRID 1808859 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1)#[N:2].[CH3:12][NH:13][C@@H:14]([CH2:22][CH2:23][CH3:24])[CH2:15][N:16]1[CH2:20][CH2:19][C@H:18]([OH:21])[CH2:17]1>C(Cl)Cl>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([N:13]([C@@H:14]([CH2:22][CH2:23][CH3:24])[CH2:15][N:16]2[CH2:20][CH2:19][C@H:18]([OH:21])[CH2:17]2)[CH3:12])=[O:8])=[CH:5][CH:4]=1)#[N:2]

Participants

4

Reactant 2

HCID 801724-Cyanobenzoyl chlorideHCID 67774204HCID 67774204, compound

Product 1

HCID 67774340HCID 67774340, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Cyanobenzoyl chloride (0.800 g, 4.83 mmol) was added to a solution of (S)-1-((S)-2-(methylamino)pentyl)pyrrolidin-3-ol (Compound J7) (1 g, 5.37 mmol) and TEA (1.496 mL, 10.74 mmol) in DCM (25 mL) at 0° C. The reaction was stirred for 30 min and was then allowed to attain rt. After 1.5 h the reaction was quenched with K2CO3 (1 M aq., 25 mL) and the aqueous phase was extracted with DCM. The organic phases were pooled, dried (MgSO4), filtered and evaporated. The residue was dissolved in EtOAc and poured on an SCX-2 column (10 g). The column was washed with EtOAc and MeOH, The product was eluted with NH3 saturated MeOH. The crude product (1.200 g, 70.9%) was obtained as a yellow oil. A fraction of the crude material was purified by preparative HPLC to yield 31 mg of the title product with a purity of 99.5%. 1H NMR (400 MHz, CD3OD) δ 0.85-1.09, 1.14-1.75, 2.03-2.23, 2.29-2.61, 2.66-2.76, 2.82-3.00, 4.24-4.39, 5.49, 7.57-7.65, 7.80-7.85. HRMS (M+H)+: calculated 316.2025. found 316.2038.

Workup

  1. customto attain rt
  2. customAfter 1.5 h the reaction was quenched with K2CO3 (1 M aq., 25 mL)
  3. extractionthe aqueous phase was extracted with DCM
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe residue was dissolved in EtOAc
  8. additionpoured on an SCX-2 column (10 g)
  9. washThe column was washed with EtOAc and MeOH
  10. washThe product was eluted with NH3 saturated MeOH
  11. customThe crude product (1.200 g, 70.9%) was obtained as a yellow oil
  12. customA fraction of the crude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-26e8fde7de064cf08a120bb64a5e3de9
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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