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

HRID 1853014Notes

Reaction equation

HRID 1853014 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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:53][C:54]([F:60])([F:59])[CH2:55][C:56](O)=[O:57].CCN(C(C)C)C(C)C>CN(C=O)C.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]([C:56](=[O:57])[CH2:55][C:54]([F:60])([F:59])[F:53])[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

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27779723,3,3-Trifluoropropionic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)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 hydrochloride

Product 1

HCID 674550662-(3-(4-(7-(1-Methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(3,3,3-trifluoropropanoyl)azetidin-3-yl)acetonitrileYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

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, 50.0 mg, 0.116 mmol) and HATU (52.8, 0.139 mmol) in dry DMF (0.50 mL) was added 3,3,3-trifluoropropanoic acid (19.3 mg, 0.150 mmol) and the mixture was stirred at ambient temperature for 2 minutes. DIEA (80.6 μL, 0.463 mmol) was added and the resulting homogeneous solution was stirred at ambient temperature for 18 hours. The reaction mixture was added to H2O (5.0 mL) and extracted with EtOAc. The combined extracts were washed with H2O, saturated aqueous NaHCO3 and dried over MgSO4. The solution was eluted through a silica gel column eluting with EtOAc then with 10% MeOH/EtOAc. The 10% MeOH/EtOAc pool was concentrated to give the title compound (32 mg, 59% yield) as a white solid. MS (apci) m/z=470.2 (M+H).

Workup

  1. stirringthe resulting homogeneous solution was stirred at ambient temperature for 18 hours
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with H2O, saturated aqueous NaHCO3
  4. dry with materialdried over MgSO4
  5. washThe solution was eluted through a silica gel column
  6. washeluting with EtOAc
  7. concentrationThe 10% MeOH/EtOAc pool was concentrated

Sources & evidence

ORD record
ord-0ed19fa73d414931b213194c0fb5762d
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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