Trimethylaluminum → N-(2-Hydroxymethylthiazolo[5,4-b]pyrid-6-yl)-5-trifluoromethyl-1-[(3-methylphenyl)methyl]-1H-indole-2-carboxamide

HRID 1911246Notes

Reaction equation

HRID 1911246 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=1)[C:7]([C:20](OCC)=[O:21])=[CH:6]2.CC(C)(C)C([O:31][CH2:32][C:33]1[S:34][C:35]2[C:40]([N:41]=1)=[CH:39][C:38]([NH2:42])=[CH:37][N:36]=2)=O.C[Al](C)C>C1(C)C=CC=CC=1.Cl>[OH:31][CH2:32][C:33]1[S:34][C:35]2[C:40]([N:41]=1)=[CH:39][C:38]([NH:42][C:20]([C:7]1[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=3)[C:9]3[C:5]([CH:6]=1)=[CH:4][C:3]([C:2]([F:1])([F:26])[F:25])=[CH:11][CH:10]=3)=[O:21])=[CH:37][N:36]=2

Participants

6

Reactant 3

HCID 16682925TrimethylaluminumHCID 58125487(6-Aminothiazolo[5,4-b]pyridin-2-yl)methyl pivalateHCID 66890014Ethyl 5-trifluoromethyl-1-[(3-methylphenyl)methyl]-1H-indole-2-carboxylate

Product 1

HCID 66888517N-(2-Hydroxymethylthiazolo[5,4-b]pyrid-6-yl)-5-trifluoromethyl-1-[(3-methylphenyl)methyl]-1H-indole-2-carboxamideYield 39.8%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 150 mg (0.415 mmol) of ethyl 5-trifluoromethyl-1-[(3-methylphenyl)methyl]-1H-indole-2-carboxylate prepared according to the protocol described in the preceding step and 132 mg (0.498 mmol) of (6-amino-thiazolo[5,4-b]pyrid-2-yl)methyl 2,2-dimethylpropanoate, obtained in step 4.2, in 1.5 mL of dry toluene, maintained under an inert atmosphere, is added dropwise, at 0° C., 0.31 mL (0.623 mmol) of a trimethylaluminium solution (2M/toluene). The reaction mixture is stirred at 110° C. for 15 hours and then concentrated to dryness. The crude reaction product is then diluted with normal hydrochloric acid solution. The product is extracted with ethyl acetate and then purified by chromatography on a column of silica, eluting with a mixture of heptane and ethyl acetate, to give 82 mg of the expected product.

Workup

  1. temperaturemaintained under an inert atmosphere
  2. additionis added dropwise, at 0° C.
  3. concentrationconcentrated to dryness
  4. customThe crude reaction product
  5. extractionThe product is extracted with ethyl acetate
  6. custompurified by chromatography on a column of silica
  7. washeluting with a mixture of heptane and ethyl acetate

Sources & evidence

ORD record
ord-4b4edbe31fbe48fb83dd2c73dfe10c02
Source dataset
uspto-grants-2013_12
Patent number
US08604050B2

Reaction notes

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