Water → HCID 117856534, compound

HRID 2284821Notes

Reaction equation

HRID 2284821 reaction equation
[CH3:1][N:2]([CH3:45])[CH2:3]/[CH:4]=[CH:5]/[C:6]([N:8]([C@@H:10]([CH3:44])[C:11]([NH:13][CH2:14][CH2:15][CH2:16][C:17]#[C:18][C:19]1[C:20]([NH:40][CH2:41][CH2:42][CH3:43])=[N:21][C:22]([NH:25][C:26]2[CH:34]=[C:33]3[C:29]([CH:30]=[N:31][N:32]3C(OCC)=O)=[CH:28][CH:27]=2)=[N:23][CH:24]=1)=[O:12])[CH3:9])=[O:7].O1CCCC1.[OH-].[Li+].O>C(OCC)(=O)C>[NH:32]1[C:33]2[C:29](=[CH:28][CH:27]=[C:26]([NH:25][C:22]3[N:21]=[C:20]([NH:40][CH2:41][CH2:42][CH3:43])[C:19]([C:18]#[C:17][CH2:16][CH2:15][CH2:14][NH:13][C:11](=[O:12])[C@@H:10]([N:8]([CH3:9])[C:6](=[O:7])/[CH:5]=[CH:4]/[CH2:3][N:2]([CH3:1])[CH3:45])[CH3:44])=[CH:24][N:23]=3)[CH:34]=2)[CH:30]=[N:31]1

Participants

6

Reactant 4

HCID 962WaterHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 90052380HCID 90052380, compound

Product 1

HCID 117856534HCID 117856534, compoundYield 64.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To (S,E)-ethyl 6-((5-(5-(2-(4-(dimethylamino)-N-methyl-2-butenamido)propaneamido)-1-pentyn-1-yl)-4-(propylamino)pyrimidin-2-yl)amino)-1H-indazole-1-carboxylate (21-23, 17.3 mg), tetrahydrofuran (1.0 mL) and 1.0 mol/L aqueous lithium hydroxide (1.0 mL) were added at room temperature, and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture, water and ethyl acetate were added. The organic layer was separated, washed with saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent, 100 to 90% ethyl acetate in methanol) to obtain (S,E)-N-(1-((5-(2 -((1H-indazol-6-yl)amino)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)-4-(dimethylamino)-N-methyl-2-butenamide (21-53, 9.8 mg) as pale yellow solid.

Workup

  1. customThe organic layer was separated
  2. washwashed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 100 to 90% ethyl acetate in methanol)

Sources & evidence

ORD record
ord-9e5e3cc8fb1340d9bc6ee297b8fb58a6
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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