4-Methylmorpholine → N-[(E)-3-(3-Methyl-4-oxo-1-n-propyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-n-propoxy-cinnamoyl]morpholine

HRID 1532071Notes

Reaction equation

HRID 1532071 reaction equation
[CH3:1][C:2]1[C:10]2[C:9](=[O:11])[NH:8][C:7]([C:12]3[CH:13]=[C:14]([CH:20]=[CH:21][C:22]=3[O:23][CH2:24][CH2:25][CH3:26])/[CH:15]=[CH:16]/[C:17](O)=[O:18])=[N:6][C:5]=2[N:4]([CH2:27][CH2:28][CH3:29])[N:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.CN1CCOCC1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH3:1][C:2]1[C:10]2[C:9](=[O:11])[NH:8][C:7]([C:12]3[CH:13]=[C:14]([CH:20]=[CH:21][C:22]=3[O:23][CH2:24][CH2:25][CH3:26])/[CH:15]=[CH:16]/[C:17]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[O:18])=[N:6][C:5]=2[N:4]([CH2:27][CH2:28][CH3:29])[N:3]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 8083MorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 135448235(E)-3-(3-Methyl-4-oxo-1-n-propyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-n-propoxycinnamic acid

Product 1

HCID 135532857N-[(E)-3-(3-Methyl-4-oxo-1-n-propyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-n-propoxy-cinnamoyl]morpholineYield 63.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (E)-3-(3-methyl-4-oxo-1-n-propyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-n-propoxycinnamic acid (Example 13; 1.0 g, 0.0025 mol) and morpholine (0.21 g, 0.0025 mol) in dichloromethane at 0° C. was added, sequentially, N-methylmorpholine (0.5 g, 0.005 mol), 1-hydroxybenzotriazole hydrate (0.383 g, 0.0025 mol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.957 g, 0.005 mol). The reaction mixture was allowed to warm to room temperature, stirred for 20 hours and evaporated under vacuum, then the residue partitioned between water (30 ml) and dichloromethane (30 ml). The organic phase was removed and the aqueous phase extracted with more dichloromethane (2×30 ml); the combined organic solutions were then dried (Na2SO4 and the solvent removed under vacuum to give a white solid. Purification by column chromatography (SiO2, CH2Cl2 then 3% MeOH in CH2Cl2) and crystallisation from ethyl acetate-hexane-methanol afforded the title compound as white crystals (0.74 g, 63%), m.p. 156-157° C. Found: C, 64.60; H, 6.85; N, 15.16. C25H31N5O4 requires C, 64.50; H,, 6.71; N, 15.04%.

Workup

  1. customevaporated under vacuum
  2. customthe residue partitioned between water (30 ml) and dichloromethane (30 ml)
  3. customThe organic phase was removed
  4. extractionthe aqueous phase extracted with more dichloromethane (2×30 ml)
  5. dry with materialthe combined organic solutions were then dried (Na2SO4
  6. customthe solvent removed under vacuum
  7. customto give a white solid
  8. customPurification by column chromatography (SiO2, CH2Cl2
  9. custom3% MeOH in CH2Cl2) and crystallisation from ethyl acetate-hexane-methanol

Sources & evidence

ORD record
ord-140413e2b9b347c88a0a62bbc44f87fd
Source dataset
uspto-grants-2001_03
Patent number
US06200980B1

Reaction notes

Loading…