Hydrochloric Acid → 2-[4-(1H-indazol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamide

HRID 914680Notes

Reaction equation

HRID 914680 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH:18]2[C:27]3[N:23]([C:24]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[N:25][N:26]=3)[C:22]3[CH:34]=[CH:35][CH:36]=[CH:37][C:21]=3[N:20]([CH2:38][C:39](=[O:50])[N:40]([CH:47]([CH3:49])[CH3:48])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:19]2=[O:51])=[N:9]1)=O)(C)(C)C.Cl>O1CCOCC1.CCOC(C)=O>[NH:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH:18]2[C:27]3[N:23]([C:24]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[N:25][N:26]=3)[C:22]3[CH:34]=[CH:35][CH:36]=[CH:37][C:21]=3[N:20]([CH2:38][C:39]([N:40]([CH:47]([CH3:48])[CH3:49])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[O:50])[C:19]2=[O:51])=[N:9]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 69314041HCID 69314041, compound

Product 1

HCID 1784578832-[4-(1H-indazol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamideYield 66.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 3-{6-[(isopropyl-phenyl-carbamoyl)-methyl]-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl}-indazole-1-carboxylic acid tert-butyl ester (391.9 mg, 0.674 mmol) in dioxane (8 mL) was added 4M HCl in dioxane (6 mL). The reaction was stirred at room temperature for 24 hours and was diluted with EtOAc. The organic solution was washed with aqueous NaHCO3 and brine, was dried (MgSO4), filtered and concentrated in vacuo. Purification by medium pressure chromatography eluting with a solvent gradient (EtOAc to 10% MeOH in EtOAc) provided 260.9 mg of 2-[4-(1H-indazol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-N-isopropyl-N-phenyl-acetamide as a racemic mixture. 1H NMR (CD3OD) δ 7.90 (d, 1H), 7.65 (d, 2H), 7.34-7.54 (m, 12H), 7.22 (t, 1H), 7.13 (t, 1H), 6.99 (d, 1H), 4.74 (m, 1H), 465 (d, 1H), 4.42 (t, 1H), 3.92-4.12 (m, 3H), 0.99 (m, 6H); MS 582.7 (M+1), 580.4 (M−1).

Workup

  1. washThe organic solution was washed with aqueous NaHCO3 and brine
  2. dry with materialwas dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by medium pressure chromatography
  6. washeluting with a solvent gradient (EtOAc to 10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-6f2315158df44ef7a427f8a1aaea4970
Source dataset
uspto-grants-2007_09
Patent number
US07265104B2

Reaction notes

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