4-Methylmorpholine → HCID 68157593, compound

HRID 242987Notes

Reaction equation

HRID 242987 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:14]([NH2:15])=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=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:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=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 12588337N2-(3-Chlorophenyl)-2,3-pyridinediamine

Product 1

HCID 68157593HCID 68157593, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N2-(3-chlorophenyl)pyridine-2,3-diamine (29 mg, 0.13 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (27 mg, 0.15 mmol), HOAt (20 mg, 0.15 mmol), 4-methylmorpholine (32 μL, 0.29 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (28 mg, 0.15 mmol) in DCM (5 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 solution of NaHCO3. The organic fraction was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting {(S)-1-[2-(3-chlorophenylamino)pyridin-3-ylcarbamoyl]ethyl}carbamic acid tert-butyl ester, as a brown oil (44 mg), was dissolved in AcOH (3 mL) and heated at 70° C. for 4 h. After cooling to RT, the volatiles were removed in vacuo. The resulting residue was partitioned between EtOAc and a saturated aqueous solution of NaHCO3. The organic fraction was washed water, followed by brine, then 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 (35 mg, 72% over two steps). LCMS (Method C): RT 3.34 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. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting {(S)-1-[2-(3-chlorophenylamino)pyridin-3-ylcarbamoyl]ethyl}carbamic acid tert-butyl ester, as a brown oil (44 mg), was dissolved in AcOH (3 mL)
  8. temperatureheated at 70° C. for 4 h
  9. temperatureAfter cooling to RT
  10. customthe volatiles were removed in vacuo
  11. customThe resulting residue was partitioned between EtOAc
  12. washThe organic fraction was washed 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-8b618eaee2d648d192e7370dc37a6188
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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