4-Methylmorpholine → [(S)-1-(2-cyclopropylamino-4-fluorophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester

HRID 242952Notes

Reaction equation

HRID 242952 reaction equation
[CH:1]1([NH:4][C:5]2[C:6]([NH2:12])=[CH:7][CH:8]=[C:9]([F:11])[CH:10]=2)[CH2:3][CH2:2]1.[C:13]([O:17][C:18]([NH:20][C@@H:21]([CH3:25])[C:22](O)=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:13]([O:17][C:18](=[O:19])[NH:20][C@H:21]([C:22](=[O:23])[NH:12][C:6]1[CH:7]=[CH:8][C:9]([F:11])=[CH:10][C:5]=1[NH:4][CH:1]1[CH2:3][CH2:2]1)[CH3:25])([CH3:14])([CH3:15])[CH3:16]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 545925541-N-cyclopropyl-5-fluorobenzene-1,2-diamine

Product 1

HCID 68158026[(S)-1-(2-cyclopropylamino-4-fluorophenylcarbamoyl)ethyl]carbamic acid tert-butyl esterYield 72.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N2-cyclopropyl-4-fluorobenzene-1,2-diamine (0.724 g, 4.4 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (0.91 g, 4.8 mmol), HOAt (0.65 g, 4.8 mmol), 4-methylmorpholine (1.1 mL, 9.7 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.92 g, 4.8 mmol) in DCM (15 mL) was stirred at RT for 18 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic fraction was washed with brine, dried (MgSO4), concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane) to afford [(S)-1-(2-cyclopropylamino-4-fluorophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester as a brown oil (1.07 g, 72%). LCMS (Method B): RT 3.40 min [M+H]+ 338.2. 110180243

Workup

  1. customThe reaction mixture was partitioned between DCM
  2. washThe organic fraction was washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-11c1fc4c2c844991acc6e0bf423310b9
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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