Hydrochloric Acid → HCID 66721057, compound

HRID 244063Notes

Reaction equation

HRID 244063 reaction equation
[Cl:1][C:2]1[C:3]([C:9]2[C:10]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([O:25][CH2:26][CH2:27][CH2:28][N:29]([CH3:31])[CH3:30])[CH:19]=3)=[N:11][C:12]([C:15](O)=[O:16])=[CH:13][CH:14]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:63][C:64]1([C:70]([OH:72])=[O:71])[CH2:69][CH2:68][CH2:67][CH2:66][CH2:65]1.Cl>CN1C(=O)CCC1.C(#N)C.O.C(Cl)Cl.CO>[ClH:1].[Cl:1][C:2]1[C:3]([C:9]2[C:10]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([O:25][CH2:26][CH2:27][CH2:28][N:29]([CH3:30])[CH3:31])[CH:19]=3)=[N:11][C:12]([C:15]([NH:63][C:64]3([C:70]([OH:72])=[O:71])[CH2:69][CH2:68][CH2:67][CH2:66][CH2:65]3)=[O:16])=[CH:13][CH:14]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 13661-Aminocyclohexanecarboxylic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 66841260HCID 66841260, compound2×

Product 1

HCID 66721057HCID 66721057, compoundYield 100.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 1.49 g (3.1 mmol) of 3,5-dichloro-2′-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-2,3′-bipyridine-6′-carboxylic acid in 15 mL of anhydrous NMP are added under argon 1.62 mL (9.3 mmol) of DIEA and 2.83 g (8.82 mmol) of TBTU. In parallel, a mixture of 421 mg (2.94 mmol) of 1-aminocyclohexanecarboxylic acid and 1.51 mL (6.19 mmol) of BSA in 15 mL of anhydrous acetonitrile is brought to 90° C. with stirring and under argon. After 2 hours, the medium dissolves completely and the solution is cooled to room temperature and then added to the solution of 3,5-dichloro-2′-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-2,3′-bipyridine-6′-carboxylic acid activated with TBTU. After stirring for 2 hours at room temperature, 10 mL of aqueous 0.5N HCl solution are added and stirring is continued for 18 hours. The reaction medium is then poured into a mixture of 100 mL of 9/1 DCM/MeOH and 10 mL of water. After extraction, the aqueous phase is again extracted with 10 mL of a 9/1 DCM/MeOH mixture. The organic phases are combined, dried over Na2SO4 and concentrated under reduced pressure. The residue is then purified by reverse-phase HPLC (RP18) using an aqueous 10−2N HCl/acetonitrile gradient of from 5% to 100% acetonitrile. After concentrating under reduced pressure and freeze-drying, 1 g of 1-{[(3,5-dichloro-2′-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-2,3′-bipyridin-6′-yl)carbonyl]amino}cyclohexanecarboxylic acid hydrochloride is obtained in the form of a white powder.

Workup

  1. customis brought to 90° C.
  2. dissolutionthe medium dissolves completely
  3. stirringAfter stirring for 2 hours at room temperature
  4. stirringstirring
  5. waitis continued for 18 hours
  6. extractionAfter extraction
  7. extractionthe aqueous phase is again extracted with 10 mL of a 9/1 DCM/MeOH mixture
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is then purified by reverse-phase HPLC (RP18)
  11. concentrationAfter concentrating under reduced pressure
  12. customfreeze-drying

Sources & evidence

ORD record
ord-243a8356bdd649d5aa518da593473e2b
Source dataset
uspto-grants-2014_02
Patent number
US08653276B2

Reaction notes

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