Hydrochloric Acid → 1-(3-acetylamino-4-hydroxybenzyl)-4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

HRID 133616Notes

Reaction equation

HRID 133616 reaction equation
O1CCOCC1.Cl.[C:8]([NH:11][C:12]1[CH:13]=[C:14]([CH:46]=[CH:47][C:48]=1[OH:49])[CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([CH2:22][NH:23][C:24](=[O:45])[CH2:25][NH:26][C:27](=[O:44])[C:28]2[CH:33]=[C:32]([F:34])[C:31]([F:35])=[CH:30][C:29]=2[NH:36]C(OC(C)(C)C)=O)[CH2:18][CH2:17]1)(=[O:10])[CH3:9]>CO>[C:8]([NH:11][C:12]1[CH:13]=[C:14]([CH:46]=[CH:47][C:48]=1[OH:49])[CH2:15][N:16]1[CH2:17][CH2:18][CH:19]([CH2:22][NH:23][C:24](=[O:45])[CH2:25][NH:26][C:27](=[O:44])[C:28]2[CH:33]=[C:32]([F:34])[C:31]([F:35])=[CH:30][C:29]=2[NH2:36])[CH2:20][CH2:21]1)(=[O:10])[CH3:9]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 184261931-(3-acetylamino-4-hydroxybenzyl)-4-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

Product 1

HCID 184261871-(3-acetylamino-4-hydroxybenzyl)-4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 4 M dioxane solution of HCl (0.50 mL) was added to a methanol (1 mL) solution of the 1-(3-acetylamino-4-hydroxybenzyl)-4-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine obtained above, and the resulting solution was stirred at room temperature overnight and concentrated. The resulting residue was then dissolved in methanol, loaded onto a Varian™ SCX column, washed with methanol (5 mL×2), eluted with a 2 M methanol solution of NH3 (5 mL), concentrated and then purified by preparative TLC (SiO2, ethyl acetate/methanol=3:2) to thereby afford 1-(3-acetylamino-4-hydroxybenzyl)-4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine (Compd. No. 2148) (2.3 mg, 9.2%). The purity was determined by RPLC/MS (98%). ESI/MS m/e 490.3 (M++H, C24H29F2N5O4).

Workup

  1. customobtained above, and the resulting solution
  2. concentrationconcentrated
  3. dissolutionThe resulting residue was then dissolved in methanol
  4. washwashed with methanol (5 mL×2)
  5. washeluted with a 2 M methanol solution of NH3 (5 mL)
  6. concentrationconcentrated
  7. custompurified by preparative TLC (SiO2, ethyl acetate/methanol=3:2) to thereby afford 1-(3-acetylamino-4-hydroxybenzyl)-4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine (Compd. No

Sources & evidence

ORD record
ord-8f50ab79e52040bdaaefe237949ad8b1
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Reaction notes

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