Hydrochloric Acid → (S)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluoro-N-(2-(3-(methylamino)piperidin-1-yl)-5-(trifluoromethyl)phenyl)benzamide

HRID 502696Notes

Reaction equation

HRID 502696 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:11]=[CH:12][C:13]([F:44])=[C:14]([CH:43]=2)[C:15]([NH:17][C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=2[N:28]2[CH2:33][CH2:32][CH2:31][C@H:30]([N:34](C)[C:35](=O)OC(C)(C)C)[CH2:29]2)=[O:16])=[CH:4][N:3]=1.Cl.C(Cl)Cl.[OH-].[Na+]>O1CCOCC1.CCOC(C)=O.CO>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:8]#[C:9][C:10]2[CH:11]=[CH:12][C:13]([F:44])=[C:14]([CH:43]=2)[C:15]([NH:17][C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:25])[F:26])[CH:21]=[CH:20][C:19]=2[N:28]2[CH2:33][CH2:32][CH2:31][C@H:30]([NH:34][CH3:35])[CH2:29]2)=[O:16])=[CH:6][N:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 16109030(S)-tert-butyl 1-(2-(5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluorobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate

Product 1

HCID 16109020(S)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluoro-N-(2-(3-(methylamino)piperidin-1-yl)-5-(trifluoromethyl)phenyl)benzamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a yellow solution of (S)-tert-butyl 1-(2-(5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluorobenzamido)-4-(trifluoromethyl)phenyl)piperidin-3-yl(methyl)carbamate (0.397 g, 0.65 mmol) in 3 mL dioxane at 0 deg. C. was added hydrogen chloride 4.0 M in dioxane (1.6 ml, 6.5 mmol). The reaction was allowed to warm to ambient temp, as the clump, which formed would not go into solution. 3 mL of CH2Cl2, was added followed by 5 mL MeOH to give a homogenous yellow solution. After 30 min, the solution was concentrated in vacuo to give a yellow solid, which was treated with 1N NaOH and EtOAc. The organic layer was washed twice with 1N NaOH, dried over anhyd. Na2SO4, filtered, and concentrated in vacuo to give (S)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-2-fluoro-N-(2-(3-(methylamino)piperidin-1-yl)-5-(trifluoromethyl)phenyl)benzamide as a light yellow solid. MS m/z=513 [M+H]+. Calc'd for C26H24F4N6O: 512.

Workup

  1. customat 0 deg. C
  2. customformed would not
  3. customto give a homogenous yellow solution
  4. concentrationthe solution was concentrated in vacuo
  5. customto give a yellow solid, which
  6. washThe organic layer was washed twice with 1N NaOH
  7. customdried over anhyd
  8. filtrationNa2SO4, filtered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9b21bd28187246b988010ec4b953c6c0
Source dataset
uspto-grants-2010_08
Patent number
US07776869B2

Reaction notes

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