4-Methylmorpholine → 3-((S)-2-tertbutoxycarbonylaminopropionylamino)-6-fluoro-2-phenylaminobenzoic acid methyl ester

HRID 242978Notes

Reaction equation

HRID 242978 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([NH2:11])[C:5]=1[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:20]([O:24][C:25]([NH:27][C@@H:28]([CH3:32])[C:29](O)=[O:30])=[O:26])([CH3:23])([CH3:22])[CH3:21].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:19])[C:4]1[C:9]([F:10])=[CH:8][CH:7]=[C:6]([NH:11][C:29](=[O:30])[C@@H:28]([NH:27][C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH3:32])[C:5]=1[NH:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 681583503-Amino-6-fluoro-2-phenylaminobenzoic acid methyl ester

Product 1

HCID 681575523-((S)-2-tertbutoxycarbonylaminopropionylamino)-6-fluoro-2-phenylaminobenzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-amino-6-fluoro-2-phenylaminobenzoic acid methyl ester (2.0 g, 7.7 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (1.6 g, 8.45 mmol), HOAt (760 mg, 8.45 mmol), 4-methylmorpholine (1.86 mL, 16.9 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.07 g, 8.45 mmol) in DCM (20 mL) was stirred at RT for 2 h. The reaction mixture was then partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane) to afford 3-((S)-2-tertbutoxycarbonylaminopropionylamino)-6-fluoro-2-phenylaminobenzoic acid methyl ester. LCMS (Method B): RT 3.65 min [M+H]+ 432.3.

Workup

  1. customThe reaction mixture was then partitioned between DCM
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-86bdd0ea99d1454585917667b4ac67b8
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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