Dicyclohexylcarbodiimide → 4-Chloro-2-{[3-(pyridin-4-yl)-1,2,4-oxadiazol-5-yl]methyl}-5-{[(1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]amino}pyridazin-3(2H)-one

HRID 2092123Notes

Reaction equation

HRID 2092123 reaction equation
[Cl:1][C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]([OH:12])=O)[N:5]=[CH:4][C:3]=1[NH:13][C@@H:14]1[CH2:19][C@@H:18]2[CH2:20][C@@H:16]([C:17]2([CH3:22])[CH3:21])[C@H:15]1[CH3:23].O[N:25]=[C:26]([C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1)[NH2:27].C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[Cl:1][C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]2[O:12][N:27]=[C:26]([C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)[N:25]=2)[N:5]=[CH:4][C:3]=1[NH:13][C@@H:14]1[CH2:19][C@@H:18]2[CH2:20][C@@H:16]([C:17]2([CH3:22])[CH3:21])[C@H:15]1[CH3:23]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 15326N'-Hydroxypyridine-4-carboximidamideHCID 68431445[5-chloro-6-oxo-4-{[(1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]amino}pyridazin-1(6H)-yl]acetic acid

Product 1

HCID 684316234-Chloro-2-{[3-(pyridin-4-yl)-1,2,4-oxadiazol-5-yl]methyl}-5-{[(1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]amino}pyridazin-3(2H)-oneYield 75.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To [5-chloro-6-oxo-4-{[(1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]amino}pyridazin-1(6H)-yl]acetic acid (80 mg, 0.235 mmol) in dichloromethane (3 mL), N′-hydroxypyridine-4-carboximidamide (38.6 mg, 0.281 mmol) and N,N′-dicyclohexylcarbodiimide (58.2 mg, 0.282 mmol) were added and stirred at room temperature for 18 hours. After completion of the reaction, the solid was filtered off with chloroform, and the filtrate was evaporated under reduced pressure. The resulting oil in toluene (2 mL) was stirred at 110° C. for 5 hours and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/4) to give the desired product (78 mg, 75% yield).

Workup

  1. customAfter completion of the reaction
  2. filtrationthe solid was filtered off with chloroform
  3. customthe filtrate was evaporated under reduced pressure
  4. stirringThe resulting oil in toluene (2 mL) was stirred at 110° C. for 5 hours
  5. customthe solvent was evaporated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/4)

Sources & evidence

ORD record
ord-8eeb461e7c7c4b029350a4b044efa544
Source dataset
uspto-grants-2013_05
Patent number
US08440666B2

Reaction notes

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