HCID 66840965, compound → HCID 66840981, compound

HRID 244073Notes

Reaction equation

HRID 244073 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([C:15]([NH:17][C@H:18]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:19][C:20](O)=[O:21])=[O:16])[CH:12]=[CH:11][C:10]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])=[CH:5][C:4]=1[O:34][CH2:35][CH2:36][CH2:37][N:38]([CH3:40])[CH3:39]>C1COCC1.CO>[ClH:2].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([C:15]([NH:17][C@@H:18]([CH2:19][CH2:20][OH:21])[C:23]([CH3:24])([CH3:26])[CH3:25])=[O:16])[CH:12]=[CH:11][C:10]=2[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])=[CH:5][C:4]=1[O:34][CH2:35][CH2:36][CH2:37][N:38]([CH3:40])[CH3:39]

Participants

4

Reactant 1

HCID 66840965HCID 66840965, compound

Product 1

HCID 66840981HCID 66840981, compoundYield 41.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 250 mg (0.42 mmol) of (3S)-3-({[6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2-methylphenyl)pyridin-2-yl]carbonyl}amino)-4,4-dimethylpentanoic acid hydrochloride (Example 6.1) in 2 mL of THF are added dropwise, under argon, 1.06 mL (2.12 mmol) of a 2N borane/dimethyl sulfide complex solution in THF. The reaction medium is stirred for 16 hours at room temperature and then diluted in 10 mL of anhydrous methanol. The solution obtained is concentrated under reduced pressure and the residue is taken up in 20 mL of methanol and then concentrated again under reduced pressure. The residue obtained is then dissolved in 20 mL of a 1/1 THF/aqueous 1N HCl solution mixture and the solution is refluxed for 4 hours. After cooling and concentrating under reduced pressure, the residue is purified by reverse-phase HPLC (RP18), eluting with a 10−2N HCl/acetonitrile gradient of from 0 to 100% acetonitrile over 120 minutes. After concentrating under reduced pressure and freeze-drying, 50 mg of 6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-N-[(1S)-1-(2-hydroxyethyl)-2,2-dimethylpropyl]-5-(2-methylphenyl)pyridine-2-carboxamide hydrochloride are obtained in the form of a white powder.

Workup

  1. customThe solution obtained
  2. concentrationis concentrated under reduced pressure
  3. concentrationconcentrated again under reduced pressure
  4. customThe residue obtained
  5. temperaturethe solution is refluxed for 4 hours
  6. temperatureAfter cooling
  7. concentrationconcentrating under reduced pressure
  8. customthe residue is purified by reverse-phase HPLC (RP18)
  9. washeluting with a 10−2N HCl/acetonitrile gradient of from 0 to 100% acetonitrile over 120 minutes
  10. concentrationAfter concentrating under reduced pressure
  11. customfreeze-drying

Sources & evidence

ORD record
ord-ce58cdfa04aa4087a5872ab818d076fc
Source dataset
uspto-grants-2014_02
Patent number
US08653276B2

Reaction notes

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