Imidazole → HCID 136265184, compound

HRID 510445Notes

Reaction equation

HRID 510445 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.[I-].[K+]>CN(C)C=O.[Cu]I.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH:29]1[CH:33]=[CH:32][N:31]=[C:30]1[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

Participants

7

Reactant 3

HCID 795ImidazoleHCID 4875Potassium IodideHCID 71532471HCID 71532471, compound

Product 1

HCID 136265184HCID 136265184, compoundYield 33.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

Three 5 mL microwave vials were charged 7-chloro-2-methyl-5-(4-morpholinyl)-3-(1-naphthalenylmethyl) pyrazolo[1,5-a]pyrimidine (50 mg, 0.127 mmol), imidazole (130 mg, 1.909 mmol), potassium iodide (42.3 mg, 0.255 mmol), copper(I) iodide (48.5 mg, 0.255 mmol) and palladium(II) acetate (8.57 mg, 0.038 mmol) in N,N-Dimethylformamide (DMF) (0.75 mL). The reaction was purged with nitrogen, sonicated for 3 min and subjected to microwave irradiation at 185° C. for 10 min. The reactions were combined and filtered through a pad of celite. The filter pad was washed with DCM (10 mL×4), and the filtrate was concentrated. Two products with same molecular weight were detected. The residue was purified by reversed phase HPLC (10˜90% CH3CN (0.1% TFA)/Water (0.1% TFA)) to give the product (18 mg, 11%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (s, 3H) 3.68 (m, 4H) 3.70-3.76 (m, 4H) 4.39 (s, 2H) 7.17-7.55 (m, 7H) 7.77 (d, J=8.08 Hz, 1H) 7.86-7.94 (m, 1H) 8.45-8.53 (m, 1H) 12.95 (s, 1H); LC/MS: MS (ES+) m/e 425.0 [M+H]+.

Workup

  1. customThe reaction was purged with nitrogen
  2. customsonicated for 3 min
  3. customirradiation at 185° C. for 10 min
  4. filtrationfiltered through a pad of celite
  5. washThe filter pad was washed with DCM (10 mL×4)
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by reversed phase HPLC (10˜90% CH3CN (0.1% TFA)/Water (0.1% TFA))

Sources & evidence

ORD record
ord-8d323ce54ee94e2599834b90ee6620ab
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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