Hydrochloric Acid → 2-(3-(4-(7-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochloride

HRID 1853012Notes

Reaction equation

HRID 1853012 reaction equation
[C:1]([CH2:3][C:4]1([N:15]2[CH:19]=[C:18]([C:20]3[N:25]4[CH:26]=[CH:27][N:28]=[C:24]4[CH:23]=[C:22]([C:29]4[CH:30]=[N:31][N:32]([CH3:34])[CH:33]=4)[N:21]=3)[CH:17]=[N:16]2)[CH2:7][N:6](C(OC(C)(C)C)=O)[CH2:5]1)#[N:2].[ClH:35]>O1CCOCC1>[ClH:35].[CH3:34][N:32]1[CH:33]=[C:29]([C:22]2[N:21]=[C:20]([C:18]3[CH:17]=[N:16][N:15]([C:4]4([CH2:3][C:1]#[N:2])[CH2:7][NH:6][CH2:5]4)[CH:19]=3)[N:25]3[CH:26]=[CH:27][N:28]=[C:24]3[CH:23]=2)[CH:30]=[N:31]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 53497465tert-butyl 3-(cyanomethyl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate

Product 1

HCID 674570102-(3-(4-(7-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile hydrochlorideYield 103%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent3×

Procedure

A 5 L 4-neck flask was equipped with an overhead stirrer and purged with N2. To this was added tert-butyl 3-(cyanomethyl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate (Example 61; 60.83 g, 132.4 mmol) and dioxane (661.9 mL, 132.4 mmol) and the flask was placed in a cool water bath. 4N HCl in dioxane (661.9 mL, 2648 mmol) was added in a fast stream. An additional 50 mL of dioxane was added to wash down the sides. The reaction stalled after 2 hours, so another 140 mL of HCl in dioxane was added. After 4 hours, another 50 mL of HCl in dioxane was added to drive to completion. The solids were filtered, washed with dioxane, and then washed with Et2O. The resultant solids were dried under high vacuum to afford 76 g (77% by weight, 103% yield) of the title compound as a powdery white solid. MS (apci) m/z=360.2 (M+H).

Workup

  1. customA 5 L 4-neck flask was equipped with an overhead stirrer
  2. custompurged with N2
  3. customthe flask was placed in a cool water bath
  4. washto wash down the sides
  5. additionso another 140 mL of HCl in dioxane was added
  6. waitAfter 4 hours
  7. additionanother 50 mL of HCl in dioxane was added
  8. filtrationThe solids were filtered
  9. washwashed with dioxane
  10. washwashed with Et2O
  11. customThe resultant solids were dried under high vacuum

Sources & evidence

ORD record
ord-81197a35c8bc4fc2a769731234840464
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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