4-Methylmorpholine → HCID 136339908, compound

HRID 1714836Notes

Reaction equation

HRID 1714836 reaction equation
C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl.[CH2:30]([C:32]1[C:33]([OH:55])=[CH:34][C:35]([OH:54])=[C:36]([C:38]2[C:39]([C:46]3[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=3)=[C:40]([C:43]([OH:45])=O)[NH:41][N:42]=2)[CH:37]=1)[CH3:31].[C:56]([NH:63][CH2:64][CH2:65][CH2:66][NH2:67])([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57]>C(Cl)Cl>[CH2:30]([C:32]1[C:33]([OH:55])=[CH:34][C:35]([OH:54])=[C:36]([C:38]2[C:39]([C:46]3[CH:47]=[CH:48][C:49]([O:52][CH3:53])=[CH:50][CH:51]=3)=[C:40]([C:43]([NH:67][CH2:66][CH2:65][CH2:64][NH:63][C:56](=[O:57])[O:58][C:59]([CH3:61])([CH3:60])[CH3:62])=[O:45])[NH:41][N:42]=2)[CH:37]=1)[CH3:31]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2735700tert-Butyl (3-aminopropyl)carbamateHCID 136378337HCID 136378337, compound

Product 1

HCID 136339908HCID 136339908, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

HOBT (572 mg, 4.2 mmol), NMM (1.55 ml, 14.1 mmol) and EDAC.HCl (820 mg, 4.3 mmol) were added at 0° C. consecutively to a solution of 5-(5-ethyl-2,4-dihydroxy-phenyl)-4-(4-methoxyphenyl)-2H-pyrazole-3-carboxylic acid (500 mg, 1.4 mmol) in 40 ml of dry DCM. The resulting mixture was stirred at 0° C. for 15 minutes. Then a solution of N—BOC-1,3-diaminopropane (740 mg, 4.3 mmol) in 5 ml of dry DCM was added. The resulting mixture was stirred at 0° C. for one our and at room temperature for 2.5 hours. The reaction mixture was washed with 50 ml of 10% w/v aqueous citric acid solution, 50 ml 20% aqueous KHCO3 solution and 50 ml of distilled water. The organic extracts were dried over MgSO4 and evaporated under reduced pressure. The crude material was purified by automated column chromatography on a 40 g RediSep™ normal phase silica cartridge using an ISCO Companion™ eluting with a mixture of 5% methanol in DCM was used. The fractions containing the desired product were combined and evaporated under reduced pressure go give the title compound as a white solid (450 mg, 63%); 1H NMR Spectrum: δH (400 MHz, DMSO-d6) 0.90 (3H t, J=7.5 Hz), 1.38 (9H, s), 1.56 (2H t, J=6.9 Hz), 2.28 (2H q, J=7.4 Hz), 2.95 (2H d, J=6.1 Hz), 3.15-3.20 (2H, m), 3.72 (3H, s), 6.41 (1H, s), 6.57 (2H, s), 6.72 (1H, s br), 6.78 (2H d, J=7.3 Hz), 7.12-7.14 (2H, m), 7.92-8.02 (1H, m br), 9.28-9.35 (2H, m), 12.89 (1H, s, br);

Workup

  1. stirringThe resulting mixture was stirred at 0° C. for one our and at room temperature for 2.5 hours
  2. washThe reaction mixture was washed with 50 ml of 10%
  3. dry with materialThe organic extracts were dried over MgSO4
  4. customevaporated under reduced pressure
  5. customThe crude material was purified by automated column chromatography on a 40 g RediSep™ normal phase silica cartridge
  6. washeluting with a mixture of 5% methanol in DCM
  7. additionThe fractions containing the desired product
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-0be82237c6e74a27ae9e6b83fa7d7e5a
Source dataset
uspto-grants-2010_09
Patent number
US07799781B2

Reaction notes

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