Tert-butoxycarbonylalanine → [(S)-1-(6-Fluoro-2,3,4,5-tetrahydro-1H-benzo[b]azepin-9-ylcarbamoyl)ethyl]carbamic acid tert-butyl ester

HRID 243208Notes

Reaction equation

HRID 243208 reaction equation
[F:1][C:2]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[C:5]([NH2:13])=[CH:4][CH:3]=1.[C:14]([O:18][C:19]([NH:21][C@@H:22]([CH3:26])[C:23](O)=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:14]([O:18][C:19](=[O:20])[NH:21][C@H:22]([C:23](=[O:24])[NH:13][C:5]1[C:6]2[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]=2[C:2]([F:1])=[CH:3][CH:4]=1)[CH3:26])([CH3:15])([CH3:16])[CH3:17]

Participants

6

Reactant 4

HCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 681578656-Fluoro-2,3,4,5-tetrahydro-1H-benzo[B]azepin-9-amine

Product 1

HCID 68158139[(S)-1-(6-Fluoro-2,3,4,5-tetrahydro-1H-benzo[b]azepin-9-ylcarbamoyl)ethyl]carbamic acid tert-butyl esterYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled mixture of 6-fluoro-2,3,4,5-tetrahydro-1H-benzo[b]azepin-9-ylamine=(195 mg, 1.0826 mmol), (S)-2-tert-butoxycarbonylaminopropionic acid (225 mg, 1.19 mmol) and HOAt (147 mg, 1.083 mmol) in DCM (10 mL) was added EDCI HCl (249 mg, 1.3 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 pink gum (270.6 mg, 71%). LCMS (Method J): RT 3.26 min [M+H]+ 352

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-4edb7b5278cc46e7bda616deac5c7872
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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