Triethylamine → [(S)-1-(2-Chloro-6-phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester

HRID 242793Notes

Reaction equation

HRID 242793 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:3]=1[NH2:15].[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH3:28])[C:25](O)=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.CCN(CC)CC>C(Cl)Cl>[C:16]([O:20][C:21](=[O:22])[NH:23][C@H:24]([C:25](=[O:26])[NH:15][C:3]1[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])[CH3:28])([CH3:17])([CH3:18])[CH3:19]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 214506083-Chloro-N1-phenylbenzene-1,2-diamine

Product 1

HCID 68157659[(S)-1-(2-Chloro-6-phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 3-chloro-N1-phenylbenzene-1,2-diamine (1.72 g, 7.87 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (1.64 g, 8.65 mmol), HOAt (1.18 g, 8.65 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.66 g, 8.65 mmol) in DCM (40 mL) cooled to 0° C. under a nitrogen atmosphere was added Et3N (3.3 mL, 0.0236 mol). The reaction mixture was stirred at 0° C. for 5 min, then slowly warmed to RT and stirring was continued for 16 h. The resulting mixture was partitioned between DCM and a saturated solution of NaHCO3. The organic layer was washed with brine, then dried (Na2SO4) and concentrated in vacuo. The residue thus obtained was purified column chromatography (Si—PCC, gradient 0-2% 2M NH3/MeOH in DCM) affording [(S)-1-(2-Chloro-6-phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester as an off-white solid (1.60 g, 52% over three steps). LCMS: RT 3.75 min [M+H]+ 390.2.

Workup

  1. temperatureslowly warmed to RT
  2. stirringstirring
  3. waitwas continued for 16 h
  4. customThe resulting mixture was partitioned between DCM
  5. washThe organic layer was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue thus obtained
  9. customwas purified column chromatography (Si—PCC, gradient 0-2% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-5e071b6c54e2457684c1a36b81f32df4
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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