1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178428373, compound

HRID 1713765Notes

Reaction equation

HRID 1713765 reaction equation
[H-].[Na+].[NH2:3][C:4]1[O:8][N:7]=[C:6]([CH3:9])[CH:5]=1.[CH:10]1C=C(OC(OC2N=CC=CC=2)=S)N=CC=1.[NH:26]([C:28](=[O:49])[C:29]([NH:31][C:32]1[CH:37]=[CH:36][C:35]([C@H:38]2[CH2:43][CH2:42][C@H:41]([CH2:44][C:45]([O:47]C)=[O:46])[CH2:40][CH2:39]2)=[CH:34][CH:33]=1)=[O:30])[NH2:27].CCN=C=NCCCN(C)C>C1COCC1.CN(C=O)C>[CH3:9][C:6]1[CH:5]=[C:4]([NH:3][C:10]2[O:49][C:28]([C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([C@H:38]4[CH2:43][CH2:42][C@H:41]([CH2:44][C:45]([OH:47])=[O:46])[CH2:40][CH2:39]4)=[CH:34][CH:33]=3)=[O:30])=[N:26][N:27]=2)[O:8][N:7]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 24758Sodium hydrideHCID 845905-Amino-3-methylisoxazoleHCID 719784O,O-Dipyridin-2-yl carbonothioateHCID 178500682HCID 178500682, compound2×

Product 1

HCID 178428373HCID 178428373, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

Sodium hydride (50 mg of a 60% dispersion in mineral oil, 1.25 mmol) was added to a stirred solution of 5-amino-3-methylisoxazole in THF. After 5 minutes di-2-pyridyl thionocarbonate (290 mg, 1.25 mmol) was added. Stirring was continued for a further 10 minutes then methyl [trans-4-(4-{[hydrazino(oxo)acetyl]amino}phenyl)cyclo-hexyl]acetate (Intermediate 43) (333 mg, 1.00 mmol) was added followed by DMF (5 mL). The mixture heated to 85° C. for 15 minutes then EDAC (240 mg, 1.25 mmol) was added. After a further 1 h at 85° C. volatile material was removed by evaporation and the residue was redissolved in MeOH (5 mL), THF (2.5 mL) and NaOH (3 mL of a 2M aqueous solution) and stirred for 16 h. The reaction mixture was concentrated under reduced pressure then redissolved in water (10 mL) and acidified with HCl (2M aqueous solution) to ca pH 5. The resulting precipitate was centrifuged, washed with water, dried under reduced pressure and triturated with ether to give the title compound (83 mg, 20%) as a solid; 1H NMR δ 1.02-1.20 (m, 2H), 1.36-1.54 (m, 2H), 1.65-1.88 (m, 5H), 2.13 (d, 2H), 2.24 (s, 3H), 2.39-2.48 (m, 1H), 6.10 (s, 1H), 7.24 (d, 2H), 7.69 (d, 2H), 11.00 (s, 1H), 12.11 (s, 1H); MS m/e MH+ 426.

Workup

  1. customAfter a further 1 h at 85° C. volatile material was removed by evaporation
  2. dissolutionthe residue was redissolved in MeOH (5 mL)
  3. stirringTHF (2.5 mL) and NaOH (3 mL of a 2M aqueous solution) and stirred for 16 h
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. dissolutionthen redissolved in water (10 mL)
  6. washwashed with water
  7. customdried under reduced pressure
  8. customtriturated with ether

Sources & evidence

ORD record
ord-b8b45cacda5e4f4b85a438a56a672370
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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