4-Methylmorpholine → HCID 68157293, compound

HRID 242988Notes

Reaction equation

HRID 242988 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:14]([NH2:15])=[CH:13][CH:12]=[CH:11][N:10]=2)=[CH:4][CH:3]=1.[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH3:28])[C:25](O)=O)=[O:22])([CH3:19])([CH3:18])[CH3:17].C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:16]([O:20][C:21](=[O:22])[NH:23][C@H:24]([C:25]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:14]2[N:15]=1)[CH3:28])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 124454222-N-(4-Chlorophenyl)pyridine-2,3-diamine

Product 1

HCID 68157293HCID 68157293, compoundYield 91.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N2-(4-chlorophenyl)pyridine-2,3-diamine (64 mg, 0.291 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (61 mg, 0.32 mmol), HOAt (44 mg, 0.32 mmol), 4-methylmorpholine (70 μL, 0.641 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (61 mg, 0.32 mmol) in DCM (10 mL) was stirred at RT for 1 h then left standing at RT for 64 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic fraction was washed with brine, dried and concentrated in vacuo. The resulting {(S)-1-[2-(4-chlorophenylamino)pyridin-3-ylcarbamoyl]ethyl}carbamic acid tert-butyl ester, as a brown oil (136 mg), was dissolved in AcOH (5 mL) and heated at 70° C. for 4 h. After cooling to RT, the volatiles were removed under reduced pressure. The resulting residue was partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic fraction was washed with water, followed by brine, dried (Na2SO4) and concentrated in vacuo. The resulting brown oil was purified by column chromatography (Si—PCC, gradient 0-5% MeOH in DCM) to afford the title compound as an orange/brown oil (99 mg, 91% over two steps). LCMS (Method C): RT 3.33 min [M+H]+ 373.2.

Workup

  1. waitthen left
  2. waitstanding at RT for 64 h
  3. customThe reaction mixture was partitioned between DCM
  4. washThe organic fraction was washed with brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting {(S)-1-[2-(4-chlorophenylamino)pyridin-3-ylcarbamoyl]ethyl}carbamic acid tert-butyl ester, as a brown oil (136 mg), was dissolved in AcOH (5 mL)
  8. temperatureheated at 70° C. for 4 h
  9. temperatureAfter cooling to RT
  10. customthe volatiles were removed under reduced pressure
  11. customThe resulting residue was partitioned between EtOAc
  12. washThe organic fraction was washed with water
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated in vacuo
  15. customThe resulting brown oil was purified by column chromatography (Si—PCC, gradient 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-6ac7f2a436ee40beb2d3accb65a02752
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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