Acetonitrile → 2-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(2,2,3,3,3-pentafluoropropyl)azetidin-3-yl)acetonitrile

HRID 1853019Notes

Reaction equation

HRID 1853019 reaction equation
Cl.[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([C:19]4([CH2:23][C:24]#[N:25])[CH2:22][NH:21][CH2:20]4)[CH:18]=3)[N:11]3[CH:26]=[CH:27][N:28]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1.C(#N)C.C(N(CC)CC)C.FC(F)(F)S(O[CH2:45][C:46]([F:52])([F:51])[C:47]([F:50])([F:49])[F:48])(=O)=O>>[CH3:2][N:3]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]3[CH:15]=[N:16][N:17]([C:19]4([CH2:23][C:24]#[N:25])[CH2:22][N:21]([CH2:45][C:46]([F:52])([F:51])[C:47]([F:50])([F:49])[F:48])[CH2:20]4)[CH:18]=3)[N:11]3[CH:26]=[CH:27][N:28]=[C:10]3[CH:9]=2)[CH:5]=[N:4]1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 27760192,2,3,3,3-Pentafluoropropyl trifluoromethanesulfonateHCID 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 hydrochloride

Product 1

HCID 866853172-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(2,2,3,3,3-pentafluoropropyl)azetidin-3-yl)acetonitrileYield 5.9%

Conditions

Temperature
45 °C

Procedure

To a solution of 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 (Example 62; 30.0 mg, 0.0694 mmol) in acetonitrile (694 μL, 0.0694 mmol) was added triethylamine (38.7 μL, 0.278 mmol) and 2,2,3,3,3-pentafluoropropyl trifluoromethanesulfonate (39.1 mg, 0.139 mmol). The reaction mixture was heated to 45° C. for 2 hours. The crude reaction mixture was purified by reverse phase HPLC to afford 2-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(2,2,3,3,3-pentafluoropropyl)azetidin-3-yl)acetonitrile (2.0 mg, 5.9% yield). MS (apci) m/z=492.2 (M+H).

Workup

  1. customThe crude reaction mixture
  2. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-bed7d7a8f1eb4277917fba75240c4cef
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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