1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-{(1E)-3-Oxo-3-[3-(pyridin-4-ylmethoxy)azetidin-1-yl]prop-1-en-1-yl}pyridin-2-amine

HRID 633925Notes

Reaction equation

HRID 633925 reaction equation
Cl.[NH2:2][C:3]1[N:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]([OH:13])=O)=[CH:5][CH:4]=1.Cl.Cl.[NH:16]1[CH2:19][CH:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=2)[CH2:17]1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C>[O:13]=[C:11]([N:16]1[CH2:19][CH:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=2)[CH2:17]1)/[CH:10]=[CH:9]/[C:6]1[CH:5]=[CH:4][C:3]([NH2:2])=[N:8][CH:7]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 66967187(E)-3-(6-aminopyrid-3-yl)acrylic acid hydrochlorideHCID 671547314-[(Azetidin-3-yloxy)methyl]pyridine dihydrochloride

Product 1

HCID 529505295-{(1E)-3-Oxo-3-[3-(pyridin-4-ylmethoxy)azetidin-1-yl]prop-1-en-1-yl}pyridin-2-amineYield 33%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of (2E)-3-(6-aminopyridin-3-yl)acrylic acid hydrochloride (42 mg, 0.21 mmol; which may be prepared as described in Step 2) in DMF (5 mL) were added 4-[(azetidin-3-yloxy)methyl]pyridine dihydrochloride (50 mg, 0.25 mmol; which may be prepared as described in Step 4), DIPEA (171 μL, 1.04 mmol), DMAP (2.5 mg, 0.02 mmol) and EDAC (48 mg, 0.25 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to dryness. The residue was partitioned between a NaHCO3 5% solution and DCM. The aqueous phase was extracted twice with DCM, dried over sodium sulfate, filtered and concentrated under vacuum to give an orange solid. The crude was purified on preparative TLC (eluent: 90/10 DCM/MeOH+1% NH4OH) to give the title compound (21 mg, 33%) as a pale yellow solid.

Workup

  1. concentrationconcentrated to dryness
  2. customThe residue was partitioned between a NaHCO3 5% solution and DCM
  3. extractionThe aqueous phase was extracted twice with DCM
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto give an orange solid
  8. customThe crude was purified on preparative TLC (eluent: 90/10 DCM/MeOH+1% NH4OH)

Sources & evidence

ORD record
ord-ea321c8b0e3b4e4aa19c227902efc669
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

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