4-Methylmorpholine → [(S)-2-benzyloxy-1-(4-fluoro-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester

HRID 242923

Reaction equation

HRID 242923 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([NH2:8])=[CH:6][CH:7]=1.[CH2:16]([O:23][CH2:24][C@H:25]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:26](O)=[O:27])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:33]([O:32][C:30](=[O:31])[NH:29][C@H:25]([C:26](=[O:27])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:24][O:23][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)([CH3:34])([CH3:36])[CH3:35]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 90234L-Serine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 214506204-Fluoro-2-phenylaminoaniline

Product 1

HCID 68157903[(S)-2-benzyloxy-1-(4-fluoro-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-fluoro-N2-phenylbenzene-1,2-diamine (550 mg, 2.7 mmol), (S)-3-benzyloxy-2-tertbutoxycarbonylaminopropionic acid (880 mg, 3.0 mmol), HOAt (410 mg, 3.0 mmol), 4-methylmorpholine (0.65 mL, 5.9 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (580 mg, 3.0 mmol) in DCM (13 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)-2-benzyloxy-1-(4-fluoro-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester as a red oil (1.1 g, 83%).

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-389e164620624889823bebcf7749ba27
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Linked notes

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