Hydrochloric Acid → HCID 69020952, compound

HRID 2091972Notes

Reaction equation

HRID 2091972 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([NH:26][C:27]([CH:29]5[CH2:33][CH2:32][CH2:31][N:30]5C([O-])=O)=[O:28])=[CH:22][CH:21]=4)[CH:17]=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.O1CCOC[CH2:39]1>C(OCC)(=O)C.CO>[CH3:39][C@@:29]1([C:27]([NH:26][C:23]2[CH:22]=[CH:21][C:20]([C:18]3[CH:17]=[CH:16][N:15]=[C:14]([NH:13][C:10]4[CH:9]=[CH:8][C:7]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)=[CH:12][CH:11]=4)[N:19]=3)=[CH:25][CH:24]=2)=[O:28])[CH2:33][CH2:32][CH2:31][NH:30]1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 312751,4-Dioxane2×HCID 86636634([(4-{2-[(4-Morpholin-4-ylphenyl)amino]pyrimidin-4-yl}-phenyl)amino]carbonyl}pyrrolidine-1-carboxylate

Product 1

HCID 69020952HCID 69020952, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,1-Dimethylethyl (2R)-2-{([(4-{2-[(4-morpholin-4-ylphenyl)amino]pyrimidin-4-yl}-phenyl)amino]carbonyl}pyrrolidine-1-carboxylate (0.38 g, 0.698 mmoles), was dissolved in an ethyl acetate (10 ml) and methanol (2 ml) mixture. 4 M hydrogen chloride in 1,4-dioxane (1.75 ml, 6.98 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 (0.87, 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), followed by diethyl ether (3×25 ml) and dried under reduced pressure to give of 0.264 mg 2-methyl-N-(4-{2-[(4-morpholin-4-ylphenyl)amino]-pyrimidin-4-yl}phenyl)prolinamide (68% 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)
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-15726524091349f6af67ff7410af6769
Source dataset
uspto-grants-2013_05
Patent number
US08440663B2

Reaction notes

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