Diisopropylethylamine → HCID 86685341, compound

HRID 1853083Notes

Reaction equation

HRID 1853083 reaction equation
[F:1][C:2]([F:7])(F)[C:3](O)=O.FC(F)(F)C(O)=O.[O:15]1[CH2:18][CH:17]([N:19]2[CH:23]=[C:22]([C:24]3[N:29]=[C:28]([C:30]4[CH:31]=[N:32][N:33]([C:35]5([CH2:39][C:40]#[N:41])[CH2:38][NH:37][CH2:36]5)[CH:34]=4)[N:27]4[CH:42]=[CH:43][N:44]=[C:26]4[CH:25]=3)[CH:21]=[N:20]2)[CH2:16]1.FC(F)(F)S(OCC(F)F)(=O)=O.C(N(C(C)C)C(C)C)C>CN(C=O)C>[F:1][CH:2]([F:7])[CH2:3][N:37]1[CH2:36][C:35]([CH2:39][C:40]#[N:41])([N:33]2[CH:34]=[C:30]([C:28]3[N:27]4[CH:42]=[CH:43][N:44]=[C:26]4[CH:25]=[C:24]([C:22]4[CH:21]=[N:20][N:19]([CH:17]5[CH2:16][O:15][CH2:18]5)[CH:23]=4)[N:29]=3)[CH:31]=[N:32]2)[CH2:38]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 86685339HCID 86685339, compound

Product 1

HCID 86685341HCID 86685341, compoundYield 12.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(3-(4-(7-(1-(Oxetan-3-yl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile bis(2,2,2-trifluoroacetate) (0.080 g, 0.089 mmol), 2,2-difluoroethyl trifluoromethanesulfonate (0.038 g, 0.178 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.093 mL, 0.534 mmol) were suspended in DMF (5 mL) and stirred at ambient temperature for 1 hour. The reaction mixture was partitioned between saturated aqueous NaHCO3 and EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography, eluting with 2.5-3.5% (9:1 MeOH:NH4OH)/DCM to provide 2-(1-(2,2-difluoro ethyl)-3-(4-(7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile (0.005 g, 0.011 mmol, 12% yield). MS (apci) m/z=466.2 (M+H).

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 and EtOAc
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude material, which
  7. customwas purified by flash column chromatography
  8. washeluting with 2.5-3.5% (9:1 MeOH:NH4OH)/DCM

Sources & evidence

ORD record
ord-26d9110513aa48d4aabaa32999ef4d7f
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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