4-Methylmorpholine → HCID 178462204, compound

HRID 242945Notes

Reaction equation

HRID 242945 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[NH:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]#[N:17])[CH2:12][CH2:11]1.[C:18]([O:22][C:23]([NH:25][C@@H:26]([CH3:30])[C:27](O)=[O:28])=[O:24])([CH3:21])([CH3:20])[CH3:19].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C1COCC1>[C:18]([O:22][C:23](=[O:24])[NH:25][C@H:26]([C:27](=[O:28])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[NH:9][C@H:10]1[CH2:11][CH2:12][C@H:13]([C:16]#[N:17])[CH2:14][CH2:15]1)[CH3:30])([CH3:19])([CH3:20])[CH3:21]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178511269HCID 178511269, compound

Product 1

HCID 178462204HCID 178462204, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of trans-4-(2-amino-5-fluorophenylamino)cyclohexanecarbonitrile (195 mg, 0.83 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (174 mg, 0.92 mmol), HOAt (125 mg, 0.92 mmol), 4-methylmorpholine (0.20 mL, 1.83 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (192 mg, 1.0 mmol) in THF (3 mL) was stirred at RT for 18 h under a nitrogen atmosphere. The reaction mixture was partitioned between EtOAc and water. The organic fraction was washed with brine, dried (MgSO4), concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a white foam (199 mg, 60%). LCMS (Method B): RT 3.37 [M+H]+ 405.2

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  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 0-50% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-efc060c30ef94202a801ea8f072a931e
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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