Triethylamine → HCID 25026790, compound

HRID 2066301Notes

Reaction equation

HRID 2066301 reaction equation
Cl.Cl.[N:3]1([CH:7]2[CH2:10][NH:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.C(N(CC)CC)C.C1([O:24][C:25](=O)[N:26]([C:36]2[CH:41]=[C:40]([O:42][C:43]3[CH:48]=[CH:47][C:46]([NH:49][C:50]([C:52]4([C:55](=[O:64])[NH:56][C:57]5[CH:62]=[CH:61][C:60]([F:63])=[CH:59][CH:58]=5)[CH2:54][CH2:53]4)=[O:51])=[C:45]([F:65])[CH:44]=3)[CH:39]=[CH:38][N:37]=2)C(OC2C=CC=CC=2)=O)C=CC=CC=1>CN(C)C=O>[N:3]1([CH:7]2[CH2:10][N:9]([C:25]([NH:26][C:36]3[CH:41]=[C:40]([O:42][C:43]4[CH:48]=[CH:47][C:46]([NH:49][C:50]([C:52]5([C:55]([NH:56][C:57]6[CH:58]=[CH:59][C:60]([F:63])=[CH:61][CH:62]=6)=[O:64])[CH2:54][CH2:53]5)=[O:51])=[C:45]([F:65])[CH:44]=4)[CH:39]=[CH:38][N:37]=3)=[O:24])[CH2:8]2)[CH2:6][CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 57470865HCID 57470865, compoundHCID 59597026[4-(3-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

Product 1

HCID 25026790HCID 25026790, compoundYield 5.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 3-(azetidin-1-yl)azetidine dihydrochloride (111 mg) in N,N-dimethylformamide (1.5 ml) was added triethylamine (0.167 ml), followed by stirring at room temperature for 15 min. A crude product of [4-(3-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (100 mg) was added thereto, followed by stirring at room temperature for 25 hr. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. This was concentrated and the residue was purified by LC-MS. Fractions containing the target compound were concentrated, and the residue was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed, and to the resultant solid (31.5 mg) was added diethyl ether (2 ml) to suspend. This was collected by filtration and washed with diethyl ether. This was dried under aeration to provide the titled compound as colorless powder (5.0 mg).

Workup

  1. stirringby stirring at room temperature for 25 hr
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationThis was concentrated
  6. customthe residue was purified by LC-MS
  7. additionFractions containing the target compound
  8. concentrationwere concentrated
  9. customthe residue was partitioned between ethyl acetate
  10. washThe organic layer was washed with brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. customThe solvent was removed
  13. additionto the resultant solid (31.5 mg) was added diethyl ether (2 ml)
  14. filtrationThis was collected by filtration
  15. washwashed with diethyl ether
  16. customThis was dried under aeration

Sources & evidence

ORD record
ord-bfda3fb6ac95425f95a162103c4d7e72
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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