1-Hydroxybenzotriazole → HCID 54596369, compound

HRID 1476461Notes

Reaction equation

HRID 1476461 reaction equation
[CH:1]([N:4]1[C:12]2[CH:11]=[C:10]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[CH:9]=[C:8]([C:19]([OH:21])=O)[C:7]=2[C:6]([CH3:22])=[N:5]1)([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH2:54][CH2:55][C:56]1[C:57](=[O:64])[NH:58][C:59]([CH3:63])=[CH:60][C:61]=1[CH3:62]>C(Cl)Cl>[CH3:62][C:61]1[CH:60]=[C:59]([CH3:63])[NH:58][C:57](=[O:64])[C:56]=1[CH2:55][NH:54][C:19]([C:8]1[C:7]2[C:6]([CH3:22])=[N:5][N:4]([CH:1]([CH3:2])[CH3:3])[C:12]=2[CH:11]=[C:10]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:9]=1)=[O:21]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 674682551-isopropyl-3-methyl-6-(pyridin-3-yl)-1H-indazole-4-carboxylic acid

Product 1

HCID 54596369HCID 54596369, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1-isopropyl-3-methyl-6-(pyridin-3-yl)-1H-indazole-4-carboxylic acid (0.5 g, 1.69 mmol) in DCM (30 mL) was added EDC.HCl (0.39 g, 2.03 mmol), HOBT (2.74 g, 2.03 mmol) followed by DIPEA (1.47 mL, 8.45 mmol) and stirred at room temperature for 15 min. To the resulting reaction mixture, 3-(amino methyl)-4,6-dimethylpyridin-2(1H)-one (0.257 g, 1.69 mmol) was added and stirred at room temperature for overnight. The reaction mixture was filtered and the precipitate was washed with water followed by ether and dried. The solid compound was further purified by silica gel chromatography (eluent: 10% MeOH in ethyl acetate) to afford the title compound as an off-white solid (225 mg, 31%). 1H NMR (DMSO-d6, 400 MHz): δ 1.461 (d, J=6.4 Hz, 6H), 2.109 (s, 3H), 2.240 (s, 3H), 2.438 (s, 3H), 4.372 (d, J=4.8 Hz, 2H), 5.042-5.107 (m, 1H), 5.870 (s, 1H), 7.410 (s, 1H), 7.501-7.533 (m, 1H), 8.061 (s, 1H), 8.215 (d, J=8 Hz, 1H), 8.461 (t, J=4.8 Hz, 1H), 8.593 (d, J=4.8 Hz, 1H), 9.036 (s, 1H), 11.489 (brs, 1H). LCMS (ES+) m/z: 430.12

Workup

  1. additionwas added
  2. stirringstirred at room temperature for overnight
  3. filtrationThe reaction mixture was filtered
  4. washthe precipitate was washed with water
  5. customdried
  6. customThe solid compound was further purified by silica gel chromatography (eluent: 10% MeOH in ethyl acetate)

Sources & evidence

ORD record
ord-c50e4df098fb40b9b1276c8eb933f541
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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