Diisopropylethylamine → 1-Acetyl-6-fluoro-3-[4-(4-methoxyphenyl)piperazin-1-ylmethyl]-1H-indazole

HRID 1956372Notes

Reaction equation

HRID 1956372 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:13])[CH:11]=2)[C:6]([CH2:14]Br)=[N:5]1)(=[O:3])[CH3:2].Cl.Cl.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1.CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:13])[CH:11]=2)[C:6]([CH2:14][N:29]2[CH2:28][CH2:27][N:26]([C:23]3[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:25][CH:24]=3)[CH2:31][CH2:30]2)=[N:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27237001-(4-Methoxyphenyl)-piperazine, dihydrochlorideHCID 228766611-Acetyl-3-bromomethyl-6-fluoro-1H-indazole

Product 1

HCID 186632381-Acetyl-6-fluoro-3-[4-(4-methoxyphenyl)piperazin-1-ylmethyl]-1H-indazoleYield 53.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

1-Acetyl-3-bromomethyl-6-fluoro-1-H-indazole (0.63 g, 2.33 mmol) in CH2Cl2 (10 mL) was treated with 4-methoxyphenylpiperazine dihydrochloride (0.593 g, 2.33 mmol) and Hunig's base (1.32 mL, 7.5 mmol) and the mixture stirred at 20° C. for 16 h. The mixture was poured into saturated aqueous sodium bicarbonate solution (25 mL) and extracted with CH2Cl2 (3×25 mL). The combined organic extracts were dried (MgSO4), concentrated and the residue purified by flash chromatography (25% EtOAc in hexane) to give the title compound as a white solid (475 mg, 53%); mp 94°-95° C. (from Et2O/hexane); 1H NMR (360 MHz, d6 -DMSO) δ8.12 (dd, J=8.4, 2.9 Hz, 1H, indazole), 8.00 (d, J=9.8 Hz, 1H, indazole), 7.34 (t, J=9.8 Hz, 1H, indazole), 6.87 (d, J=9.2 Hz, 2H, Ph), 6.80 (d, J=9.2 Hz, 2H, Ph), 3.93 (s, 2H, Ar--CH2N), 3.67 (s, 3H, OMe), 3.02 (m, 4H, piperazine), 2.70 (s, 3H, Ac), 2.63 (m, 4H, piperazine); MS (CI+) m/e 383 (M+H+); Anal. calcd for C21H23FN4O2 : C, 65.95; H, 6.06; N, 14.65. Found: C, 66.38; H, 5.79; N, 14.59.

Workup

  1. extractionextracted with CH2Cl2 (3×25 mL)
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. concentrationconcentrated
  4. customthe residue purified by flash chromatography (25% EtOAc in hexane)

Sources & evidence

ORD record
ord-dafa7b38ca374c00b282f344d03a332a
Source dataset
uspto-grants-1998_07
Patent number
US05780475

Reaction notes

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