HOAt → [(S)-1-(2-Phenylaminopyridin-3-ylcarbamoyl)propyl]carbamic acid tert-butyl ester

HRID 242896Notes

Reaction equation

HRID 242896 reaction equation
[C:1]1([NH:7][C:8]2[C:13]([NH2:14])=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15]([O:19][C:20]([NH:22][C@@H:23]([CH2:27][CH3:28])[C:24](O)=[O:25])=[O:21])([CH3:18])([CH3:17])[CH3:16].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.C(N(CC)CC)C>[C:15]([O:19][C:20](=[O:21])[NH:22][C@H:23]([C:24](=[O:25])[NH:14][C:13]1[C:8]([NH:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:9][CH:10]=[CH:11][CH:12]=1)[CH2:27][CH3:28])([CH3:16])([CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 181649HOAt2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acid2×HCID 106790912-N-phenylpyridine-2,3-diamine

Product 1

HCID 68157992[(S)-1-(2-Phenylaminopyridin-3-ylcarbamoyl)propyl]carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
0 °C

Procedure

Triethylamine (1.8 mL, 13.0 mmol) was added to a mixture of N2-phenylpyridine-2,3-diamine (800 mg, 4.32 mmol), (S)-2-tertbutoxycarbonylaminobutyric acid (960 mg, 4.75 mmol), HOAt (650 mg, 4.75 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (910 mg, 4.75 mmol) in anhydrous DCM (25 mL) at 0° C. under a nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 10 min then slowly warmed to RT. Stirring at RT was continued for 16 h. After re-cooling to 0° C., additional amounts of (S)-2-tertbutoxycarbonylaminobutyric acid (610 mg), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (580 mg), HOAt (410 mg) and triethylamine (1.0 mL) were added and stirring at RT continued for 1 h. The reaction mixture was then partitioned between DCM and a saturated aqueous solution of NaHCO3. The aqueous phase was further extracted with DCM (×3) and the combined organic fractions washed with water, dried (Na2SO4) and concentrated in vacuo to afford the title compound as a dark oil. The crude material was used without further purification in the following step. Yield assumed to be quantitative. LCMS (Method J): RT 2.67 min [M+H]+ 371.2.

Workup

  1. temperaturethen slowly warmed to RT
  2. stirringStirring at RT
  3. waitwas continued for 16 h
  4. temperatureAfter re-cooling to 0° C.
  5. stirringstirring at RT
  6. waitcontinued for 1 h
  7. customThe reaction mixture was then partitioned between DCM
  8. extractionThe aqueous phase was further extracted with DCM (×3)
  9. washthe combined organic fractions washed with water
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-19b8bf2b89c747a1b8587a27c79207e0
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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