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

HRID 243202Notes

Reaction equation

HRID 243202 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][CH2:6][NH:7]2.FC1C=CC(N)=C2C=1C=CC=N2.[C:25]([O:29][C:30]([NH:32][C@@H:33]([CH3:37])[C:34](O)=[O:35])=[O:31])([CH3:28])([CH3:27])[CH3:26].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:25]([O:29][C:30](=[O:31])[NH:32][C@H:33]([C:34](=[O:35])[NH:12][C:9]1[CH:10]=[CH:11][C:2]([F:1])=[C:3]2[C:8]=1[NH:7][CH2:6][CH2:5][CH2:4]2)[CH3:37])([CH3:26])([CH3:27])[CH3:28]

Participants

7

Reactant 5

HCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 445582645-Fluoroquinolin-8-amineHCID 681575905-Fluoro-1,2,3,4-tetrahydroquinolin-8-amine

Product 1

HCID 68157874[(S)-1-(5-fluoro-1,2,3,4-tetrahydroquinolin-8-ylcarbamoyl)ethyl]carbamic acid tert-butyl esterYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled mixture of the 5-fluoro-1,2,3,4-tetrahydroquinolin-8-ylamine and 5-fluoroquinolin-8-ylamine from the previous step (70.4 mg, 0.424 mmol), (S)-2-tert-butoxycarbonylaminopropionic acid (88.3 mg, 0.466 mmol) and HOAt (57.7 mg, 0.424 mmol) in DCM (6 mL) was added EDCI HCl (97.7 mg, 0.51 mmol). 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 purple gum (105 mg, 73%). LCMS (Method B): RT 3.35 min [M+H]+ 338.

Workup

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

Sources & evidence

ORD record
ord-76af5221586448829912e3b2957ee29c
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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