Hydrochloric Acid → HCID 69020952, compound

HRID 2091971Notes

Reaction equation

HRID 2091971 reaction equation
[CH3:1][C:2]1([C:14](=[O:41])[NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]4[CH:34]=[CH:33][C:32]([N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)=[CH:31][CH:30]=4)[N:23]=3)=[CH:18][CH:17]=2)[CH2:6][CH2:5][CH2:4][N:3]1C(OC(C)(C)C)=O.Cl.O1CCOCC1>C(OCC)(=O)C.CO>[CH3:1][C@@:2]1([C:14]([NH:15][C:16]2[CH:17]=[CH:18][C:19]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]4[CH:34]=[CH:33][C:32]([N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)=[CH:31][CH:30]=4)[N:23]=3)=[CH:20][CH:21]=2)=[O:41])[CH2:6][CH2:5][CH2:4][NH:3]1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 312751,4-Dioxane2×HCID 57991144Tert-butyl 2-methyl-2-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenylcarbamoyl)-pyrrolidine-1-carboxylate

Product 1

HCID 69020952HCID 69020952, compoundYield 0.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 2-methyl-2-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl-carbamoyl)pyrrolidine-1-carboxylate (0.140 g, 0.250 mmoles), was dissolved in an ethyl acetate (5 ml) and methanol (1 ml) mixture. 4 M hydrogen chloride in 1,4-dioxane (0.625 ml, 2.5 mmoles, 10 equivalents, purchased from Sigma-Aldrich) was then added in a drop wise fashion over 5-10 minutes. Upon completion of addition, the reaction mixture was stirred at room temperature, and the progress of the reaction monitored by LC/MS. After 16 hours, additional 4M hydrogen chloride in 1,4-dioxane (0.312 ml, 1.25 mmoles, 5 equivalents) was added. After a total of 48 hours the reaction was complete and the resulting slurry was filtered off. The reaction flask was rinsed with ethyl acetate to ensure complete transfer of product. The resulting solid was washed with ethyl acetate (3×10 ml) and diethyl ether (2×25 ml) and dried under reduced pressure to give of 0.061 mg 2-methyl-N-(4-{2-[(4-morpholin-4-ylphenyl)amino]pyrimidin-4-yl}phenyl)prolinamide 367 as its hydrochloride salt (53% yield).

Workup

  1. additionUpon completion of addition
  2. customAfter a total of 48 hours
  3. filtrationthe resulting slurry was filtered off
  4. washThe reaction flask was rinsed with ethyl acetate
  5. washThe resulting solid was washed with ethyl acetate (3×10 ml) and diethyl ether (2×25 ml)
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-ad0a691942a24fc89394291929e46939
Source dataset
uspto-grants-2013_05
Patent number
US08440663B2

Reaction notes

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