4-Methylmorpholine → [(S)-1-(4-Cyano-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester

HRID 242802Notes

Reaction equation

HRID 242802 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[C:17]([O:21][C:22]([NH:24][C@@H:25]([CH3:29])[C:26](O)=[O:27])=[O:23])([CH3:20])([CH3:19])[CH3:18].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1>C1COCC1>[C:17]([O:21][C:22](=[O:23])[NH:24][C@H:25]([C:26](=[O:27])[NH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[NH:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH3:29])([CH3:18])([CH3:19])[CH3:20]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 681572074-Amino-3-phenylaminobenzonitrile

Product 1

HCID 68157188[(S)-1-(4-Cyano-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl esterYield 89.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-amino-3-phenylaminobenzonitrile (490 mg, 2.34 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (490 mg, 2.57 mol), HOAt (380 mg, 2.79 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (540 mg, 2.81 mol) and 4-methylmorpholine (560 μL, 5.15 mmol) in THF (5 mL) was stirred at RT for 48 h under an argon atmosphere. The crude reaction mixture was then partitioned between EtOAc and a saturated solution of NaHCO3. The aqueous phase was further extracted with EtOAc and the combined organic layers were washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% EtOAc in DCM) affording [(S)-1-(4-Cyano-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester as a cream foam (800 mg, 89%). LCMS: RT 3.62 min [M+H]+ 381.2.

Workup

  1. customThe crude reaction mixture
  2. customwas then partitioned between EtOAc
  3. extractionThe aqueous phase was further extracted with EtOAc
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% EtOAc in DCM)

Sources & evidence

ORD record
ord-317ff4297ed349539b2d128df4869ec0
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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