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

HRID 1853018Notes

Reaction equation

HRID 1853018 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][CH:45]([F:47])[F:46])(=O)=O>>[F:46][CH:45]([F:47])[CH2:44][N:21]1[CH2:22][C:19]([CH2:23][C:24]#[N:25])([N:17]2[CH:18]=[C:14]([C:12]3[N:11]4[CH:26]=[CH:27][N:28]=[C:10]4[CH:9]=[C:8]([C:6]4[CH:5]=[N:4][N:3]([CH3:2])[CH:7]=4)[N:13]=3)[CH:15]=[N:16]2)[CH2:20]1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 27740892,2-Difluoroethyl trifluoromethanesulfonate2×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 hydrochloride

Product 1

HCID 866853162-(1-(2,2-difluoroethyl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrileYield 45%

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 K2CO3 (38.4 mg, 0.278 mmol) and 2,2-difluoroethyl trifluoromethanesulfonate (29.7 mg, 0.139 mmol). After heating to 45° C. for 2 hours, the reaction was incomplete and another portion of 2,2-difluoroethyl trifluoromethanesulfonate (20.0 mg, 0.0936 mmol) was added to drive to completion. Purification of the crude reaction mixture by reverse phase HPLC afforded 2-(1-(2,2-difluoroethyl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile (13.2 mg, 45% yield). MS (apci) m/z=424.2 (M+1-1).

Workup

  1. customPurification of the crude
  2. customreaction mixture by reverse phase HPLC

Sources & evidence

ORD record
ord-fcc4d96875e643f7bd0d309742040c8e
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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