Toluene → N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-4-(1-methylpiperidin-4-yl)benzamide

HRID 16804Notes

Reaction equation

HRID 16804 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14]C)=O)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:28][O:29][C:30]2[CH:31]=[C:32]([NH2:35])[NH:33][N:34]=2)[CH:23]=[C:24]([O:26][CH3:27])[CH:25]=1.C[Al](C)C.C1(C)C=CC=CC=1>>[CH3:27][O:26][C:24]1[CH:23]=[C:22]([CH2:28][O:29][C:30]2[CH:31]=[C:32]([NH:35][C:12](=[O:14])[C:11]3[CH:10]=[CH:9][C:8]([CH:5]4[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]4)=[CH:17][CH:16]=3)[NH:33][N:34]=2)[CH:21]=[C:20]([O:19][CH3:18])[CH:25]=1

Participants

5

Reactant 4

HCID 1140TolueneHCID 16682925TrimethylaluminumHCID 49760144Methyl 4-(1-methylpiperidin-4-YL)benzoateHCID 574403815-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine

Product 1

HCID 66589788N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-4-(1-methylpiperidin-4-yl)benzamideYield 46.7%

Procedure

N-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-4-(1-methylpiperidin-4-yl)benzamide was prepared following the procedure as for Example 159, but starting from methyl 4-(1-methylpiperidin-4-yl)benzoate (0.25 g, 1.07 mmol), 5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-amine (0.267 g, 1.07 mmol) and 2M trimethylaluminium in toluene (2.14 ml, 4.29 mmol). The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 8% 2.5M NH3/MeOH in DCM. Pure fractions were evaporated to dryness, redissolved in DCM, triturated with ether and evaporated to dryness to afford the title compound (0.225 g, 46.5%) as a white solid. 1H NMR (399.9 MHz, DMSO-d6) δ 1.69 (1H, d), 1.73 (2H, d), 1.77 (1H, s), 1.95-2.02 (2H, m), 2.21 (3H, s), 2.88 (2H, d), 3.76 (6H, s), 5.09 (2H, s), 5.62 (1H, s), 6.45 (1H, s), 6.60 (2H, s), 7.41-7.42 (2H, m), 7.89-7.91 (2H, m), 10.85 (1H, s), 11.58 (1H, s). MS: m/z 451 (MH+).

Workup

  1. customN-[5-[(3,5-dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-4-(1-methylpiperidin-4-yl)benzamide was prepared
  2. customThe crude product was purified by silica column chromatography
  3. washeluting with a gradient of 0 to 8% 2.5M NH3/MeOH in DCM
  4. customPure fractions were evaporated to dryness
  5. dissolutionredissolved in DCM
  6. customtriturated with ether
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-bbcfb9d481804bcfa110e74feebf5eb1
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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