Diisopropylethylamine → (S)-tert-butyl (1-((3-(2-((4-cyanophenyl)amino)-4-(propylamino)pyrimidine-5-carboxamido)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284657Notes

Reaction equation

HRID 2284657 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[C:14]([NH:16][CH2:17][CH2:18][CH3:19])[C:13]([C:20]([OH:22])=O)=[CH:12][N:11]=2)=[CH:5][CH:4]=1)#[N:2].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH2:55][C:56]1[CH:57]=[C:58]([NH:62][C:63](=[O:75])[C@@H:64]([N:66]([CH3:74])[C:67](=[O:73])[O:68][C:69]([CH3:72])([CH3:71])[CH3:70])[CH3:65])[CH:59]=[CH:60][CH:61]=1.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.CN(C)C=O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]2[N:15]=[C:14]([NH:16][CH2:17][CH2:18][CH3:19])[C:13]([C:20]([NH:55][C:56]3[CH:57]=[C:58]([NH:62][C:63](=[O:75])[C@@H:64]([N:66]([CH3:74])[C:67](=[O:73])[O:68][C:69]([CH3:70])([CH3:72])[CH3:71])[CH3:65])[CH:59]=[CH:60][CH:61]=3)=[O:22])=[CH:12][N:11]=2)=[CH:7][CH:8]=1)#[N:2]

Participants

9

Reactant 6

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 90051717(S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamateHCID 900520362-((4-Cyanophenyl)amino)-4-(propylamino)pyrimidine-5-carboxylic acid

Product 1

HCID 90052038(S)-tert-butyl (1-((3-(2-((4-cyanophenyl)amino)-4-(propylamino)pyrimidine-5-carboxamido)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamateYield 56.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To 2-((4-cyanophenyl)amino)-4-(propylamino)pyrimidine-5-carboxylic acid (C5, 297 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (383 mg) and 1-hydroxybenzotriazole monohydrate (270 mg), N,N-dimethylformamide (7.5 mL) was added at room temperature, and the mixture was stirred at 50° C. for 1 hour and 20 minutes. The reaction mixture was cooled to room temperature, and then N,N-diisopropylethylamine (697 μL) and (S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (B9, 323 mg) were added to the mixture at room temperature, and the mixture was stirred at the same temperature for 30 minutes, and then further stirred at 50° C. for 1 hour and 30 minutes. 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, washed successively with water 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 silica gel column chromatography (eluent, 40 to 10% hexane in ethyl acetate) to obtain (S)-tert-butyl (1-((3-(2-((4-cyanophenyl)amino)-4-(propylamino)pyrimidine-5-carboxamido)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (C8, 325 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred at the same temperature for 30 minutes
  3. stirringfurther stirred at 50° C. for 1 hour and 30 minutes
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customThe organic layer was separated
  6. washwashed successively with water and saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (eluent, 40 to 10% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-a991af8705c44d71a12d02107824b63a
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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