Tert-butoxycarbonylalanine → [(S)-1-(5-Fluoro-2-methyl-1,2,3,4-tetrahydroquinolin-8-ylcarbamoyl)ethyl]carbamic acid tert-butyl ester

HRID 243215Notes

Reaction equation

HRID 243215 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:9]([NH2:12])=[C:8]2[C:3]=1[CH2:4][CH2:5][CH:6]([CH3:13])[NH:7]2.FC1C=CC(N)=C2C=1C=CC(C)=N2.[C:27]([O:31][C:32]([NH:34][C@@H:35]([CH3:39])[C:36](O)=[O:37])=[O:33])([CH3:30])([CH3:29])[CH3:28].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:27]([O:31][C:32](=[O:33])[NH:34][C@H:35]([C:36](=[O:37])[NH:12][C:9]1[CH:10]=[CH:11][C:2]([F:1])=[C:3]2[C:8]=1[NH:7][CH:6]([CH3:13])[CH2:5][CH2:4]2)[CH3:39])([CH3:28])([CH3:29])[CH3:30]

Participants

7

Reactant 5

HCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 681578015-Fluoro-2-methyl-1,2,3,4-tetrahydroquinolin-8-amineHCID 681578245-Fluoro-2-methylquinolin-8-amine

Product 1

HCID 68157423[(S)-1-(5-Fluoro-2-methyl-1,2,3,4-tetrahydroquinolin-8-ylcarbamoyl)ethyl]carbamic acid tert-butyl esterYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To the mixture of 5-fluoro-2-methyl-1,2,3,4-tetrahydroquinolin-8-ylamine and 5-fluoro-2-methylquinolin-8-ylamine from the previous step (0.369 mmol) in DCM (10 mL) was added (S)-2-tert-butoxycarbonylaminopropionic acid (76.8 mg, 0.405 mmol) and HOAt (56 mg, 0.41 mmol). The mixture was cooled in an ice bath, then EDCI HCl (85 mg, 0.44 mmol) was added. The reaction mixture was stirred in the ice bath for 2 h, then diluted with DCM, washed with aqueous Na2CO3 and then water. The organic layer was dried (Na2SO4) and then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 20-50% EtOAc in cyclohexane) affording the title compound as a colourless solid (63.6 mg, 49%, 2 steps). LCMS (Method J): RT 3.40 min [M+H]+ 352

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. washwashed with aqueous Na2CO3
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 20-50% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-19cc8c1cc82c46618e5944190f884003
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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