Triethylamine → [(S)-1-(3-Cyano-4-fluoro-2-phenylaminophenylcarbamoyl)propyl]carbamic acid tert-butyl ester

HRID 243048Notes

Reaction equation

HRID 243048 reaction equation
C(N(CC)CC)C.[NH2:8][C:9]1[C:10]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:11]([C:14]([F:17])=[CH:15][CH:16]=1)[C:12]#[N:13].Cl.CN(C)CCCN=C=NCC.C1C=NC2N(O)N=NC=2C=1.[C:47]([O:51][C:52]([NH:54][C@@H:55]([CH2:59][CH3:60])[C:56](O)=[O:57])=[O:53])([CH3:50])([CH3:49])[CH3:48]>C(Cl)Cl>[C:47]([O:51][C:52](=[O:53])[NH:54][C@H:55]([C:56](=[O:57])[NH:8][C:9]1[CH:16]=[CH:15][C:14]([F:17])=[C:11]([C:12]#[N:13])[C:10]=1[NH:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[CH2:59][CH3:60])([CH3:48])([CH3:49])[CH3:50]

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 181649HOAt2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acidHCID 681579663-Amino-6-fluoro-2-phenylaminobenzonitrile

Product 1

HCID 68157031[(S)-1-(3-Cyano-4-fluoro-2-phenylaminophenylcarbamoyl)propyl]carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (0.55 mL, 3.96 mmol) was added to a stirred mixture of 3-amino-6-fluoro-2-phenylaminobenzonitrile (0.30 g, 1.32 mmol), (S)-(2-tert-butoxycarbonylamino)butyric acid (0.30 g, 1.45 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.28 g, 1.45 mmol) and HOAt (0.20 g, 1.45 mmol) in DCM at 0° C. under nitrogen. The resultant mixture was stirred at 0° C. for 5 minutes then 20° C. for 16 h. The reaction mixture was re-cooled to 0° C. and (S)-2-tert-butoxycarbonylaminobutyric acid (0.30 g, 1.45 mmol), N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide hydrochloride (0.28 g, 1.45 mmol), HOAt (0.20 g, 1.45 mmol) and triethylamine (0.55 mL, 3.96 mmol) added sequentially, and the resultant mixture stirred at 20° C. for 24 h. The mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and DCM (3×20 mL). The combined DCM extracts were washed with water, dried (Na2SO4) and concentrated in vacuo to give the title compound as an off white foam (0.64 g). LCMS (method H): Rt 2.93 min, [M+H]+ 413.

Workup

  1. customThe mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and DCM (3×20 mL)
  2. washThe combined DCM extracts were washed with water
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cf48e4ff6f8b42719b0ff6a1b3a8f4ce
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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