Diisopropylethylamine → Ethyl 2-((8-(benzyloxy)-5-(6-(tert-butoxycarbonylamino)hexylamino)-1,6-naphthyridine-7-carboxamido)methyl)-5-fluorobenzoate

HRID 455306Notes

Reaction equation

HRID 455306 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:34](O)=[O:35])=[N:11][C:12]([NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:71][CH2:72][C:73]1[CH:83]=[CH:82][C:81]([F:84])=[CH:80][C:74]=1[C:75]([O:77][CH2:78][CH3:79])=[O:76]>ClCCl>[CH2:1]([O:8][C:9]1[C:10]([C:34]([NH:71][CH2:72][C:73]2[CH:83]=[CH:82][C:81]([F:84])=[CH:80][C:74]=2[C:75]([O:77][CH2:78][CH3:79])=[O:76])=[O:35])=[N:11][C:12]([NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28])=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 671095498-(Benzyloxy)-5-(6-(tert-butoxycarbonylamino)hexylamino)-1,6-naphthyridine-7-carboxylic acidHCID 67109674Ethyl 2-(aminomethyl)-5-fluorobenzoate hydrochloride

Product 1

HCID 68009450Ethyl 2-((8-(benzyloxy)-5-(6-(tert-butoxycarbonylamino)hexylamino)-1,6-naphthyridine-7-carboxamido)methyl)-5-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

8-(Benzyloxy)-5-(6-(tert-butoxycarbonylamino)hexylamino)-1,6-naphthyridine-7-carboxylic acid (Example 1.2; 0.42 g; 0.85 mmol) was dissolved in dichloro methane (9 ml). DIPEA (0.58 ml; 3.42 mmol) and HBTU (0.39 g; 1.03 mmol) were added. The reaction mixture was stirred at room temperature during 5 min. Ethyl 2-(aminomethyl)-5-fluorobenzoate hydrochloride (Example 4; 0.24 g; 1.03 mmol) was added portionwise at room temperature. The mixture was stirred overnight at room temperature. The mixture was diluted with CH2Cl2 and washed with a saturated aqueous Na2CO3 solution (2×) and H2O. The organic layer was separated, dried (MgSO4), filtered and evaporated. The residue was purified by flash column chromategraphy over silica gel (eluent: hexane/EtOAc 10:1 up to 1:1). The fractions were collected and the solvent evaporated.

Workup

  1. stirringThe mixture was stirred overnight at room temperature
  2. washwashed with a saturated aqueous Na2CO3 solution (2×) and H2O
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash column chromategraphy over silica gel (eluent: hexane/EtOAc 10:1 up to 1:1)
  8. customThe fractions were collected
  9. customthe solvent evaporated

Sources & evidence

ORD record
ord-ab6b39bc235346a5a43bd495e862b7c7
Source dataset
uspto-grants-2013_07
Patent number
US08497270B2

Reaction notes

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