Hydrochloric Acid → HCID 66721207, compound

HRID 244066Notes

Reaction equation

HRID 244066 reaction equation
[ClH:1].[Cl:2]C1C=CC([C:9]2[C:10]([C:22]([OH:24])=O)=[N:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[CH:14]=2)=CC=1OCCCN(C)C.ON1[C:37](=[O:38])[CH2:36][CH2:35][C:34]1=O.CCN=C=N[CH2:45][CH2:46][CH2:47][N:48]([CH3:50])[CH3:49].Cl.CCN([CH:58]([CH3:60])C)C(C)C.[NH2:61][C@H:62]([C:71]([CH3:74])([CH3:73])[CH3:72])[CH2:63][C:64]([O:66]C(C)(C)C)=[O:65].Cl>CN(C=O)C.C(O)=O>[ClH:2].[Cl:1][C:58]1[CH:60]=[CH:34][C:35]([C:12]2[N:11]=[C:10]([C:22]([NH:61][C@H:62]([C:71]([CH3:72])([CH3:73])[CH3:74])[CH2:63][C:64]([OH:66])=[O:65])=[O:24])[CH:9]=[CH:14][C:13]=2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])=[CH:36][C:37]=1[O:38][CH2:45][CH2:46][CH2:47][N:48]([CH3:49])[CH3:50]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 80170N-HydroxysuccinimideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11222558HCID 11222558, compoundHCID 86697100HCID 86697100, compound

Product 1

HCID 66721207HCID 66721207, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 674 mg (1.4 mmol) of 6-{(4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2-chlorophenyl)pyridine-2-carboxylic acid hydrochloride in 7 mL of anhydrous DMF are successively added, under argon and at room temperature, 240 mg (2.1 mmol) of N-hydroxysuccinimide and 401 mg (2.1 mmol) of EDC.HCl. After stirring for 18 hours, 1.31 mL (7.7 mmol) of DIEA and 304 mg (1.51 mmol) of tert-butyl (3S)-3-amino-4,4-dimethylpentanoate (J. Org. Chem., 1999, 64, 6411-6417) are successively added to the reaction medium. Stirring is continued for 18 hours at room temperature and the reaction mixture is then concentrated under reduced pressure. The residue obtained is then treated for 18 hours at room temperature with 0.25 mL (3 mmol) of aqueous 12N HCl solution in 30 mL of formic acid and then concentrated under reduced pressure. After purification by reverse-phase HPLC(RP18), eluting with an aqueous 10−2N HCl/acetonitrile gradient of from 5% to 100% acetonitrile, and after freeze-drying, 500 mg of (3S)-3-({[6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2-chlorophenyl)pyridin-2-yl]carbonyl}amino)-4,4-dimethylpentanoic acid hydrochloride are obtained in the form of a white powder.

Workup

  1. additionare successively added, under argon and at room temperature
  2. stirringStirring
  3. waitis continued for 18 hours at room temperature
  4. concentrationthe reaction mixture is then concentrated under reduced pressure
  5. customThe residue obtained
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification by reverse-phase HPLC(RP18)
  8. washeluting with an aqueous 10−2N HCl/acetonitrile gradient of from 5% to 100% acetonitrile
  9. customafter freeze-drying

Sources & evidence

ORD record
ord-13695f367bc347b1ab8f77d4ec6363e3
Source dataset
uspto-grants-2014_02
Patent number
US08653276B2

Reaction notes

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