Sodium Bicarbonate → 4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)-N-(3-(2,2,2-trifluoro-N-methylacetamido)phenyl)pyrimidine-5-carboxamide

HRID 2284638Notes

Reaction equation

HRID 2284638 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:8]([CH3:15])[C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])[CH:5]=[CH:6][CH:7]=1.[CH2:16]([NH:19][C:20]1[C:25]([C:26](O)=[O:27])=[CH:24][N:23]=[C:22]([NH:29][CH2:30][CH2:31][C:32]2[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=2)[N:21]=1)[CH2:17][CH3:18].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.C(N(CC)CC)C.CN(C)C=O>[CH2:16]([NH:19][C:20]1[C:25]([C:26]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([N:8]([CH3:15])[C:9](=[O:14])[C:10]([F:11])([F:12])[F:13])[CH:3]=2)=[O:27])=[CH:24][N:23]=[C:22]([NH:29][CH2:30][CH2:31][C:32]2[CH:33]=[CH:34][N:35]=[CH:36][CH:37]=2)[N:21]=1)[CH2:17][CH3:18]

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22946301N-(3-aminophenyl)-2,2,2-trifluoro-N-methylactamideHCID 900517164-(Propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxylic acid

Product 1

HCID 900520024-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)-N-(3-(2,2,2-trifluoro-N-methylacetamido)phenyl)pyrimidine-5-carboxamideYield 26.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To N-(3-aminophenyl)-2,2,2-trifluoro-N-methylactamide (302 mg) synthesized according to the method described in U.S. Pat. No. 6,344,465 B1, 4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidine-5-carboxylic acid (A3, 627 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (545 mg) and 1-hydroxybenzotriazole monohydrate (377 mg), N,N-dimethylformamide (15 mL) and triethylamine (766 μL) were added at room temperature, the reaction vessel was sealed, and then the mixture was stirred at 100° C. for 40 minutes by using a microwave reaction system. The reaction mixture was cooled to room temperature, and then saturated aqueous sodium hydrogencarbonate and ethyl acetate were added to the mixture. The organic layer was separated, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 97 to 96% ethyl acetate in methanol) to obtain 4-(propylamino)-2-((2-(pyridin-4-yl)ethyl)amino)-N-(3-(2,2,2-trifluoro-N-methylacetamido)phenyl)pyrimidine-5-carboxamide (A7, 186 mg).

Workup

  1. customthe reaction vessel was sealed
  2. customa microwave reaction system
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (eluent, 97 to 96% ethyl acetate in methanol)

Sources & evidence

ORD record
ord-00da24b1dcc84df0b3c1cb3284d9ab60
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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