Hydrochloric Acid → N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indazole-4-carboxamide hydrochloride

HRID 1476457Notes

Reaction equation

HRID 1476457 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[CH:22]=[C:21]([C:23]2[CH:24]=[CH:25][C:26]([N:29]3[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30]3)=[N:27][CH:28]=2)[CH:20]=[C:19]2[C:15]=1[C:16]([CH3:45])=[N:17][N:18]2[CH:42]([CH3:44])[CH3:43])=[O:13].[ClH:46]>C(Cl)Cl.O1CCOCC1>[ClH:46].[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[C:15]2[C:16]([CH3:45])=[N:17][N:18]([CH:42]([CH3:43])[CH3:44])[C:19]=2[CH:20]=[C:21]([C:23]2[CH:28]=[N:27][C:26]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[CH:22]=1)=[O:13]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 67468774tert-butyl 4-(5-(4-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methylcarbamoyl)-1-isopropyl-3-methyl-1H-indazol-6-yl)pyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 54596366N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indazole-4-carboxamide hydrochlorideYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of tert-butyl 4-(5-(4-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methylcarbamoyl)-1-isopropyl-3-methyl-1H-indazol-6-yl)pyridin-2-yl)piperazine-1-carboxylate (250 mg, 0.407 mmol) in DCM (50 mL) was added 4M HCl in 1,4-dioxane (6 mL) at 0° C. and stirred at room temperature for 2 h. The reaction mixture was concentrated and then co-distilled with toluene (50 mL). The residue was dried under reduced pressure to get the crude HCl salt (195 mg). The residue was triturated with diethyl ether (100 mL), DCM (100 mL) and n-hexane (100 mL) to afford the title compound as a pale brown solid (135 mg, 60%). 1H NMR (DMSO-d6, 400 MHz): δ 1.454 (d, J=6.4 Hz, 6H), 2.119 (s, 3H), 2.244 (s, 3H), 2.412 (s, 3H), 3.222 (s, 4H), 3.839 (s, 4H), 4.369 (d, J=4.4 Hz, 2H), 5.005-5.071 (m, 1H), 5.888 (s, 1H), 7.125 (d, J=8.8 Hz, 1H), 7.348 (s, 1H), 7.942 (s, 1H), 8.158 (d, J=8 Hz, 1H), 8.429 (t, J=4.6 Hz, 1H), 8.613 (d, J=2.0 Hz, 1H), 9.145 (s, 2H), 11.519 (brs, 1H). LCMS (ES+): 514.24 [M+H].

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customThe residue was dried under reduced pressure
  3. customto get the crude HCl salt (195 mg)
  4. customThe residue was triturated with diethyl ether (100 mL), DCM (100 mL) and n-hexane (100 mL)

Sources & evidence

ORD record
ord-366c9745f05b4b4f814d6480ae59bcf5
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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