Tert-butoxycarbonylalanine → HCID 178462194, compound

HRID 243086Notes

Reaction equation

HRID 243086 reaction equation
[CH2:1]([O:8][C@H:9]1[CH2:12][C@H:11]([NH:13][C:14]2[C:15]([NH2:21])=[CH:16][CH:17]=[C:18]([F:20])[CH:19]=2)[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]([O:26][C:27]([NH:29][C@@H:30]([CH3:34])[C:31](O)=O)=[O:28])([CH3:25])([CH3:24])[CH3:23].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:22]([O:26][C:27](=[O:28])[NH:29][C@H:30]([C:31]1[N:13]([C@H:11]2[CH2:12][C@H:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:10]2)[C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[N:21]=1)[CH3:34])([CH3:25])([CH3:24])[CH3:23]

Participants

6

Reactant 4

HCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178507657HCID 178507657, compound

Product 1

HCID 178462194HCID 178462194, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of N2-(trans-3-benzyloxycyclobutyl)-4-fluoro-benzene-1,2-diamine (1.73 g, 2.55 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (0.54 g, 2.81 mmol) and HOAt (0.38 g, 2.81 mmol) in DCM (20 mL) were cooled to 0° C. under nitrogen atmosphere. To this mixture N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.54 g, 2.81 mmol) was added portion wise and the reaction mixture was stirred at RT for 1 h. The reaction mixture allowed to warm to RT then partitioned between DCM (30 mL) and 10% aqueous citric acid (20 mL). The organic layer was washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a off-white gum, which solidified on standing (0.88 g, 75%). NMR: 328289. LCMS (Method B): RT 3.85 min [M+H]+ 458.

Workup

  1. temperatureto warm to RT
  2. customthen partitioned between DCM (30 mL) and 10% aqueous citric acid (20 mL)
  3. washThe organic layer was washed with brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-772a8c73e9db4872b26723aea794dc7b
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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