Triethylamine → ethyl 3-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-ylcarbamoyl)imidazo[1,2-a]pyridine-7-carboxylate

HRID 79319

Reaction equation

HRID 79319 reaction equation
Cl.[CH2:2]([O:4][C:5]([C:7]1[CH:12]=[CH:11][N:10]2[C:13]([C:16]([OH:18])=O)=[CH:14][N:15]=[C:9]2[CH:8]=1)=[O:6])[CH3:3].C(N(CC)CC)C.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[CH2:38]([C:40]1[C:48]2[C:47]([NH2:49])=[CH:46][CH:45]=[CH:44][C:43]=2[N:42]([CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([CH3:57])[N:52]=2)[N:41]=1)[CH3:39]>CN1C(=O)CCC1>[CH2:38]([C:40]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][C:47]=2[NH:49][C:16]([C:13]2[N:10]3[CH:11]=[CH:12][C:7]([C:5]([O:4][CH2:2][CH3:3])=[O:6])=[CH:8][C:9]3=[N:15][CH:14]=2)=[O:18])[N:42]([CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[C:53]([CH3:57])[N:52]=2)[N:41]=1)[CH3:39]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 672598043-ethyl-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amineHCID 672610337-(Ethoxycarbonyl) imidazo[1,2-a]pyridine-3-carboxylic acid hydrochloride

Product 1

HCID 67260084ethyl 3-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-ylcarbamoyl)imidazo[1,2-a]pyridine-7-carboxylateYield 82.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
75 °C

Procedure

To 7-(ethoxycarbonyl) imidazo[1,2-a]pyridine-3-carboxylic acid hydrochloride (501 mg, 1.85 mmol) in NMP (10 mL) was added triethylamine (468 mg, 4.63 mmol). The suspension turned into a clear solution. 2,4,6-trichlorobenzoyl chloride (474 mg, 1.94 mmol) was added dropwise to the reaction mixture. A milky suspension resulted after 10 minutes. The mixture was stirred for another 30 minutes. 3-Ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (444 mg, 1.67 mmol) was added in one portion to the reaction mixture. The mixture was sealed and heated to 75° C. for 3 hours. The mixture was cooled to ambient temperature and concentrated under reduced pressure to remove NMP. The residue was diluted with EtOAc/H2O (20 mL/10 mL). The organic phase was washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. Silica gel chromatography (EtOAc/Hexane 5:1 to 10:1) provided the final product (665 mg). MS (ES+APCI) m/z=483 (M+H).

Workup

  1. customA milky suspension resulted after 10 minutes
  2. customThe mixture was sealed
  3. temperatureThe mixture was cooled to ambient temperature
  4. concentrationconcentrated under reduced pressure
  5. customto remove NMP
  6. additionThe residue was diluted with EtOAc/H2O (20 mL/10 mL)
  7. washThe organic phase was washed with H2O (5 mL) and brine (5 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-a7791ea545384506bc16423005786319
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Linked notes

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