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

HRID 1853020Notes

Reaction equation

HRID 1853020 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([O-])([O-])=O.[K+].[K+].FC(F)(F)S(O[CH2:44][C:45]([F:48])([F:47])[F:46])(=O)=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]([CH2:44][C:45]([F:48])([F:47])[F:46])[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

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl 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 674576832-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(2,2,2-trifluoro ethyl)azetidin-3-yl)acetonitrileYield 48%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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; 50 mg, 0.12 mmol) in acetonitrile (1.2 mL, 0.12 mmol) was added K2CO3 (48 mg, 0.35 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (30 mg, 0.13 mmol). The reaction mixture was heated to 45° C. for 15 hours, then cooled. After diluting in water, the mixture was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. Purification of the crude material by reverse phase HPLC using a 0-100% acetonitrile/water gradient afforded 2-(3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(2,2,2-trifluoro ethyl)azetidin-3-yl)acetonitrile (24 mg, 48.0% yield). MS (apci) m/z=442.2 (M+H).

Workup

  1. temperaturecooled
  2. extractionthe mixture was extracted with EtOAc
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the crude material by reverse phase HPLC

Sources & evidence

ORD record
ord-dd71063025aa4a0e982683aa1c8065b4
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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