Hydrochloric Acid → Abemaciclib Metabolites M2

HRID 2264367Notes

Reaction equation

HRID 2264367 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][C:18]([NH:21][C:22]3[N:27]=[C:26]([C:28]4[CH:40]=[C:39]([F:41])[C:31]5[N:32]=[C:33]([CH3:38])[N:34]([CH:35]([CH3:37])[CH3:36])[C:30]=5[CH:29]=4)[C:25]([F:42])=[CH:24][N:23]=3)=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>C(Cl)Cl.CO.O1CCOCC1>[F:42][C:25]1[C:26]([C:28]2[CH:40]=[C:39]([F:41])[C:31]3[N:32]=[C:33]([CH3:38])[N:34]([CH:35]([CH3:37])[CH3:36])[C:30]=3[CH:29]=2)=[N:27][C:22]([NH:21][C:18]2[CH:19]=[CH:20][C:15]([CH2:14][N:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[CH:16][N:17]=2)=[N:23][CH:24]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 67427599HCID 67427599, compound

Product 1

HCID 59376686Abemaciclib Metabolites M2Yield 96.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 4-{6-[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-3H-benzoimidazol-5-yl)-pyrimidin-2-ylamino]-pyridin-3-ylmethyl}-piperazine-1-carboxylic acid tert-butyl ester (150 mg) in DCM (10 mL) and methanol (10 mL) add hydrogen chloride 4M in dioxane (194 μL). Stir 10 min and remove the solvent under vacuum. Purify by strong cation exchange cartridge (SCX) eluting with methanol and then methanol-NH3 2M followed by silica gel column chromatography eluting with DCM/methanol-NH3 2M (3%) to afford 120 mg of the title compound. MS (ES+): m/z=479 (M+H)+.

Workup

  1. customremove the solvent under vacuum
  2. customPurify by strong cation exchange cartridge (SCX)
  3. washeluting with methanol
  4. washeluting with DCM/methanol-NH3 2M (3%)

Sources & evidence

ORD record
ord-4192ad56d6ec4fa8bd8794184532c1fa
Source dataset
uspto-grants-2010_12
Patent number
US07855211B2

Reaction notes

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