Imidazole → HCID 71271601, compound

HRID 510446Notes

Reaction equation

HRID 510446 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:22])[C:10]([CH2:11][C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=[CH:14][CH:13]=3)=[C:6]2[N:5]=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:3]=1.[NH:29]1[CH:33]=[CH:32][N:31]=[CH:30]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN[C@H]1[C@H](NC)CCCC1>O1CCOCC1.[Cu]I>[N:29]1([C:2]2[N:7]3[N:8]=[C:9]([CH3:22])[C:10]([CH2:11][C:12]4[C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[CH:15]=[CH:14][CH:13]=4)=[C:6]3[N:5]=[C:4]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[CH:3]=2)[CH:33]=[CH:32][N:31]=[CH:30]1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 71532471HCID 71532471, compound

Product 1

HCID 71271601HCID 71271601, compoundYield 14.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 20 mL microwave vial was charged with 7-chloro-2-methyl-5-(4-morpholinyl)-3-(1-naphthalenylmethyl) pyrazolo[1,5-a]pyrimidine (200 mg, 0.509 mmol), imidazole (243 mg, 3.56 mmol), potassium phosphate (324 mg, 1.527 mmol), copper(I) iodide (58.2 mg, 0.305 mmol) and (1R,2R)-diaminomethylcyclohexane (87 mg, 0.611 mmol) in 1,4-Dioxane (5 mL). The reaction was purged with nitrogen and sealed. The reaction mixture was stirred at 100° C. for 5 days. After cooling the reaction, EtOAc (30 mL) was added in. The reaction was filtered and the filtrate was washed with brine (10 mL×3), dried (MgSO4) and concentrated to give the crude. The residue was purified on silica column (EtOAc/Hexane: 20˜60%), then (0˜3% MeOH/DCM) to give the product (32 mg, 14%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.24 (s, 3H) 3.71 (s, 8H) 4.37 (s, 2H) 6.90 (s, 1H) 7.19 (s, 1H) 7.30-7.60 (m, 4H) 7.77 (d, J=7.83 Hz, 1H) 7.84-7.97 (m, 1H) 8.08 (t, J=1.39 Hz, 1H) 8.35-8.55 (m, 1H) 8.70 (s, 1H); LC/MS: MS (ES+) m/e 425.0 [M+H]+.

Workup

  1. customThe reaction was purged with nitrogen
  2. customsealed
  3. temperatureAfter cooling
  4. customthe reaction, EtOAc (30 mL)
  5. additionwas added in
  6. filtrationThe reaction was filtered
  7. washthe filtrate was washed with brine (10 mL×3)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customto give the crude
  11. customThe residue was purified on silica column (EtOAc/Hexane: 20˜60%)

Sources & evidence

ORD record
ord-2ab9f50160a548e79353e9c686d1cc09
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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