Diisopropylethylamine → Ethyl 2-((8-(benzyloxy)-5-(4-(4-(tert-butoxycarbonylamino)butyl)-piperazin-1-yl)-1,6-naphthyridine-7-carboxamido)methyl)-5-fluorobenzoate

HRID 455317Notes

Reaction equation

HRID 455317 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:37](O)=[O:38])=[N:11][C:12]([N:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:21][CH2:20]2)=[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.[NH2:74][CH2:75][C:76]1[CH:86]=[CH:85][C:84]([F:87])=[CH:83][C:77]=1[C:78]([O:80][CH2:81][CH3:82])=[O:79]>ClCCl>[CH2:1]([O:8][C:9]1[C:10]([C:37]([NH:74][CH2:75][C:76]2[CH:86]=[CH:85][C:84]([F:87])=[CH:83][C:77]=2[C:78]([O:80][CH2:81][CH3:82])=[O:79])=[O:38])=[N:11][C:12]([N:19]2[CH2:20][CH2:21][N:22]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])[CH2:23][CH2:24]2)=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67109674Ethyl 2-(aminomethyl)-5-fluorobenzoate hydrochlorideHCID 680093878-(Benzyloxy)-5-(4-(4-(tert-butoxycarbonylamino)butyl)piperazin-1-yl)-1,6-naphthyridine-7-carboxylic acid

Product 1

HCID 68009254Ethyl 2-((8-(benzyloxy)-5-(4-(4-(tert-butoxycarbonylamino)butyl)-piperazin-1-yl)-1,6-naphthyridine-7-carboxamido)methyl)-5-fluorobenzoateYield 96.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

8-(Benzyloxy)-5-(4-(4-(tert-butoxycarbonylamino)butyl)piperazin-1-yl)-1,6-naphthyridine-7-carboxylic acid (Example 4.2; 1.4 mmol) was dissolved in dichloro methane (14 ml). DIPEA (5.4 mmol) and HBTU (1.6 mmol) were added. The reaction mixture was stirred at room temperature during 5 min. Ethyl 2-(aminomethyl)-5-fluorobenzoate hydrochloride (Example 4; 1.6 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 chromatography over silica gel (eluent: hexane/EtOAc 10:1 up to 1:1) to afford 0.97 gr of the title compound.

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 chromatography over silica gel (eluent: hexane/EtOAc 10:1 up to 1:1)

Sources & evidence

ORD record
ord-42020425bd6344d3bfbef129792e0f39
Source dataset
uspto-grants-2013_07
Patent number
US08497270B2

Reaction notes

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