Diisopropylethylamine → Methyl 5-(4-(2-((tert-butoxycarbonylamino)methyl)-5-fluorobenzamido)-N-methylbutylsulfonamido)-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate

HRID 455314Notes

Reaction equation

HRID 455314 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][S:6]([N:9]([C:11]1[N:20]=[C:19]([C:21]([O:23][CH3:24])=[O:22])[C:18]([O:25][S:26]([C:29]2[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=2)(=[O:28])=[O:27])=[C:17]2[C:12]=1[CH:13]=[CH:14][CH:15]=[N:16]2)[CH3:10])(=[O:8])=[O:7].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.[C:69]([O:73][C:74]([NH:76][CH2:77][C:78]1[CH:86]=[CH:85][C:84]([F:87])=[CH:83][C:79]=1[C:80](O)=[O:81])=[O:75])([CH3:72])([CH3:71])[CH3:70]>ClCCl>[C:69]([O:73][C:74]([NH:76][CH2:77][C:78]1[CH:86]=[CH:85][C:84]([F:87])=[CH:83][C:79]=1[C:80]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][S:6]([N:9]([C:11]1[N:20]=[C:19]([C:21]([O:23][CH3:24])=[O:22])[C:18]([O:25][S:26]([C:29]2[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=2)(=[O:27])=[O:28])=[C:17]2[C:12]=1[CH:13]=[CH:14][CH:15]=[N:16]2)[CH3:10])(=[O:8])=[O:7])=[O:81])=[O:75])([CH3:72])([CH3:70])[CH3:71]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 110654742-[[(tert-Butoxycarbonyl)amino]methyl]-5-fluorobenzoic acidHCID 86667516Methyl 5-(4-amino-N-methylbutylsulfonamido)-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate

Product 1

HCID 86667517Methyl 5-(4-(2-((tert-butoxycarbonylamino)methyl)-5-fluorobenzamido)-N-methylbutylsulfonamido)-8-(tosyloxy)-1,6-naphthyridine-7-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 5-(4-amino-N-methylbutylsulfonamido)-8-(tosyloxy)-1,6-naphthyridine-7-carboxylate (Example 3.2; 5.52 mmol) in dichloro methane (5 mL) was added DIPEA (18.7 mmol) and HBTU (5.63 mmol). The mixture was stirred for 5 min at rt. 2((Tert-butoxycarbonylamino)methyl)-5-fluorobenzoic acid (4.69 mmol) was added portionwise at room temperature. The mixture was stirred overnight at room temperature. The solvent was evaporated. The residue was washed with a 1M Na2CO3 solution. The aqueous phase was extracted with dichloro methane, dried and was concentrated. The crude product was purified by SiO2 column chromatography (5:1 to 1:1 hexanes:ethyl acetate) to give the target compound in 49% yield.

Workup

  1. stirringThe mixture was stirred overnight at room temperature
  2. customThe solvent was evaporated
  3. washThe residue was washed with a 1M Na2CO3 solution
  4. extractionThe aqueous phase was extracted with dichloro methane
  5. customdried
  6. concentrationwas concentrated
  7. customThe crude product was purified by SiO2 column chromatography (5:1 to 1:1 hexanes:ethyl acetate)
  8. customto give the target compound in 49% yield

Sources & evidence

ORD record
ord-e0a3148aa55f4fe8bbf9e55672b0cf43
Source dataset
uspto-grants-2013_07
Patent number
US08497270B2

Reaction notes

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