Diisopropylethylamine → HCID 90052274, compound

HRID 2284725Notes

Reaction equation

HRID 2284725 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH2:17][CH3:18])[C:12]([C:19]#[C:20][C:21]3[CH:22]=[C:23]([NH:27][C:28](=[O:33])[C@@H:29]([NH:31][CH3:32])[CH3:30])[CH:24]=[CH:25][CH:26]=3)=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.Cl.[CH3:35][N:36]([CH3:43])[CH2:37]/[CH:38]=[CH:39]/[C:40](O)=[O:41].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.CN(C)C=O>[CH3:35][N:36]([CH3:43])[CH2:37]/[CH:38]=[CH:39]/[C:40]([N:31]([C@@H:29]([CH3:30])[C:28]([NH:27][C:23]1[CH:24]=[CH:25][CH:26]=[C:21]([C:20]#[C:19][C:12]2[C:13]([NH:15][CH2:16][CH2:17][CH3:18])=[N:14][C:9]([NH:8][C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:10][CH:11]=2)[CH:22]=1)=[O:33])[CH3:32])=[O:41]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 90052277HCID 90052277, compound

Product 1

HCID 90052274HCID 90052274, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To (S)—N-(3-((2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)ethynyl)phenyl)-2-(methylamino)propanamide (G3, 67 mg), 4-dimethylaminocrotonic acid hydrochloride (50 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (58 mg), N,N-dimethylformamide (1.5 mL) and N,N-diisopropylethylamine (105 μL) were added at room temperature, and the mixture was stirred at the same temperature for 13 hours. To the reaction mixture, saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, washed successively with saturated aqueous sodium hydrogencarbonate and 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 94% ethyl acetate in methanol). The obtained solid matter was washed with water, and then dried under reduced pressure to obtain (S,E)-4-(dimethylamino)-N-(1-((3-((2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)ethynyl)phenyl)amino)-1-oxopropan-2-yl)-N-methyl-2-butenamide (8-1, 50 mg).

Workup

  1. customThe organic layer was separated
  2. washwashed successively with saturated aqueous sodium hydrogencarbonate and 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 94% ethyl acetate in methanol)
  6. washThe obtained solid matter was washed with water
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-c663fb8738d84b31a8e24c41de25a499
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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