Diisopropylethylamine → HCID 66654532, compound

HRID 517782Notes

Reaction equation

HRID 517782 reaction equation
[CH3:1][C:2]1([CH3:8])[CH2:7][O:6][CH2:5][CH2:4][NH:3]1.Cl[CH2:10][C:11]1[N:15]([C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=2)[N:14]=[N:13][N:12]=1.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl.Cl.C(OCC)C>[CH3:1][C:2]1([CH3:8])[CH2:7][O:6][CH2:5][CH2:4][N:3]1[CH2:10][C:11]1[N:15]([C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=2)[N:14]=[N:13][N:12]=1

Participants

8

Reactant 3

HCID 81531DiisopropylethylamineHCID 145518493,3-DimethylmorpholineHCID 66655405HCID 66655405, compound2×

Product 1

HCID 66654532HCID 66654532, compound

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 3,3-dimethylmorpholine (49.7 mg, 0.328 mmol, commercially available, for example from Otava, Kiev, Ukraine or Tyger Scientific, Ewing, USA), 4-[5-(chloromethyl)-1H-tetrazol-1-yl]benzonitrile (60 mg, 0.273 mmol, may be prepared as described in Intermediate 10) and di-isopropylethylamine (0.110 mL, 0.628 mmol) in acetonitrile (0.7 mL) was heated to 120° C. for 30 minutes in a microwave reactor. The reaction mixture was allowed to cool and the solution purified by MDAP. Fractions containing the desired product were combined and the solvent removed. The residue was partitioned between saturated NaHCO3 (aq, 2 mL) and DCM (5 mL). The organic layer was collected via a hydrophobic frit and the solvent removed under vacuum. The residue was dissolved in a minimum of dichloromethane before the addition of 1N HCl in diethyl ether (1 mL). The compound was partitioned between saturated NaHCO3 (aq, 2 mL) and DCM (5 mL). The organic layer was collected via a hydrophobic frit and the solvent removed under vacuum. The crude product was further purified by silica chromatography (Biotage SP4, eluting 20% EtOAc in iso-hexane (3 column volumes) then a gradient from 20-60% EtOAc in iso-hexane (over 12 column volumes)) to yield a colourless gum. The residue was dissolved in a minimum of dichloromethane before the addition of 1N HCl in diethyl ether (1 mL). The solvent was removed under vacuum to yield a pale yellow solid which was triturated with methanol (0.5 mL) then dried under vacuum to yield the title compound as a white solid (22 mg).

Workup

  1. customwas heated to 120° C. for 30 minutes in a microwave reactor
  2. temperatureto cool
  3. customthe solution purified by MDAP
  4. additionFractions containing the desired product
  5. customthe solvent removed
  6. customThe residue was partitioned between saturated NaHCO3 (aq, 2 mL) and DCM (5 mL)
  7. customThe organic layer was collected via a hydrophobic frit
  8. customthe solvent removed under vacuum
  9. dissolutionThe residue was dissolved in a minimum of dichloromethane before the addition of 1N HCl in diethyl ether (1 mL)
  10. customThe compound was partitioned between saturated NaHCO3 (aq, 2 mL) and DCM (5 mL)
  11. customThe organic layer was collected via a hydrophobic frit
  12. customthe solvent removed under vacuum
  13. customThe crude product was further purified by silica chromatography (Biotage SP4
  14. washeluting 20% EtOAc in iso-hexane (3 column volumes)
  15. customa gradient from 20-60% EtOAc in iso-hexane (over 12 column volumes)) to yield a colourless gum
  16. customThe solvent was removed under vacuum
  17. customto yield a pale yellow solid which
  18. customwas triturated with methanol (0.5 mL)
  19. customthen dried under vacuum

Sources & evidence

ORD record
ord-d4ac26f9a7d746ef8e81c3274c452c88
Source dataset
uspto-grants-2015_08
Patent number
US09115132B2

Reaction notes

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