Dichloromethane → HCID 67458587, compound

HRID 1853079Notes

Reaction equation

HRID 1853079 reaction equation
[O:1]1[CH2:4][CH:3]([N:5]2[CH:9]=[C:8]([C:10]3[N:15]=[C:14]([C:16]4[CH:17]=[N:18][N:19]([C:21]5([CH2:30][C:31]#[N:32])[CH2:24][N:23]([CH2:25][C:26]([F:29])([F:28])[F:27])[CH2:22]5)[CH:20]=4)[N:13]4[CH:33]=[CH:34][N:35]=[C:12]4[CH:11]=3)[CH:7]=[N:6]2)[CH2:2]1.C([O-])(O)=O.[Na+].C(Cl)[Cl:42]>>[Cl:42][C:33]1[N:13]2[C:14]([C:16]3[CH:17]=[N:18][N:19]([C:21]4([CH2:30][C:31]#[N:32])[CH2:24][N:23]([CH2:25][C:26]([F:29])([F:28])[F:27])[CH2:22]4)[CH:20]=3)=[N:15][C:10]([C:8]3[CH:7]=[N:6][N:5]([CH:3]4[CH2:2][O:1][CH2:4]4)[CH:9]=3)=[CH:11][C:12]2=[N:35][CH:34]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 53497472HCID 53497472, compound

Product 1

HCID 67458587HCID 67458587, compoundYield 28%

Procedure

2-(3-(4-(7-(1-(Oxetan-3-yl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(2,2,2-trifluoroethyl)azetidin-3-yl)acetonitrile (Example 105; 0.040 g, 0.08274 mmol) was suspended in DCM (3 mL) and saturated aqueous NaHCO3 (1 mL). n-Chlorosuccinimide (0.017 g, 0.124 mmol) was added in one portion and the reaction mixture stirred at ambient temperature overnight. Additional n-chlorosuccinimide (0.033 g, 0.248 mmol) was added and the reaction was allowed to stir at ambient temperature overnight. The reaction mixture was partitioned between saturated aqueous NaHCO3 and DCM. 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 1-2% (9:1 MeOH:NH4OH)/DCM to provide 2-(3-(4-(3-chloro-7-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)-1-(2,2,2-trifluoroethyl)azetidin-3-yl)acetonitrile (0.012 g, 0.023 mmol, 28% yield). MS (apci) m/z=518.1 (M+H).

Workup

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

Sources & evidence

ORD record
ord-a6b459a64480454293e3bf6941582891
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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