Tert-butoxycarbonylalanine → HCID 178496641, compound

HRID 243096Notes

Reaction equation

HRID 243096 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C@H:10]2[CH2:13][C@H:12]([O:14][CH3:15])[CH2:11]2)[C:5]([NH2:8])=[CH:6][CH:7]=1.[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH3:28])[C:25](O)=O)=[O:22])([CH3:19])([CH3:18])[CH3:17].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:16]([O:20][C:21](=[O:22])[NH:23][C@H:24]([C:25]1[N:9]([C@H:10]2[CH2:11][C@H:12]([O:14][CH3:15])[CH2:13]2)[C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=2[N:8]=1)[CH3:28])([CH3:19])([CH3:18])[CH3:17]

Participants

6

Reactant 4

HCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178496652HCID 178496652, compound

Product 1

HCID 178496641HCID 178496641, compoundYield 30.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-fluoro-N2(trans-3-methoxycyclobutyl)benzene-1,2-diamine (0.36 g, 1.7 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (0.35 g, 1.9 mmol) and HOAt (0.26 g, 1.9 mmol) in DCM (8 mL) was cooled to 0° C. under a nitrogen atmosphere. To this mixture was added N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.36 g, 1.9 mmol) portion wise and the mixture stirred at RT for 1 h. The reaction mixture was allowed to warm to RT then partitioned between DCM (30 mL) and a saturated aqueous solution of NaHCO3 (20 mL). The organic fraction was washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the compound as a pink solid (0.188 g, 29%). The compound thus obtained was dissolved in AcOH (8 mL) and heated at 70° C. for 18 h. After cooling to RT, the volatiles were evaporated in vacuo and the residue partitioned between DCM (40 mL) and a saturated aqueous solution of NaHCO3 (20 mL). The organic fraction was washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resulting dark brown residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as yellow oil (0.125 g, 20%). LCMS (Method B): RT 2.84 min [M+H]+ 364.05

Workup

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

Sources & evidence

ORD record
ord-2840ac500c7646c69a0a78b498c9b6d5
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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