Diisopropylethylamine → Methyl 2-(2-(((benzyloxy)carbonyl)amino)-2-methylpropanoyl)-5-oxo-1,2,3,4,5,10-hexahydrobenzo[b][1,7]naphthyridine-6-carboxylate

HRID 521421Notes

Reaction equation

HRID 521421 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:17])([CH3:16])[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Br.[O:52]=[C:53]1[C:62]2[CH2:61][CH2:60][NH:59][CH2:58][C:57]=2[NH:56][C:55]2[CH:63]=[CH:64][CH:65]=[C:66]([C:67]([O:69][CH3:70])=[O:68])[C:54]1=2>CN(C=O)C>[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:17])([CH3:16])[C:13]([N:59]1[CH2:58][C:57]2[NH:56][C:55]3[CH:63]=[CH:64][CH:65]=[C:66]([C:67]([O:69][CH3:70])=[O:68])[C:54]=3[C:53](=[O:52])[C:62]=2[CH2:61][CH2:60]1)=[O:15])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 294936N-((Benzyloxy)carbonyl)-2-methylalanineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89657238Methyl 5-oxo-1,2,3,4,5,10-hexahydrobenzo[b][1,7]naphthyridine-6-carboxylate hydrobromide

Product 1

HCID 89657465Methyl 2-(2-(((benzyloxy)carbonyl)amino)-2-methylpropanoyl)-5-oxo-1,2,3,4,5,10-hexahydrobenzo[b][1,7]naphthyridine-6-carboxylateYield 14.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(((benzyloxy)carbonyl)amino)-2-methylpropanoic acid (385 mg, 1.62 mmol) in DMF (8.0 mL) were added HATU (1.1 g, 2.94 mmol), DIPEA (0.75 g, 5.87 mmol), and methyl 5-oxo-1,2,3,4,5,10-hexahydrobenzo[b][1,7]naphthyridine-6-carboxylate hydrobromide (410 mg, 1.6 mmol). The mixture was then stirred at room temperature for 24 h. Then the reaction was quenched by water (20 mL). The mixture was extracted with THF/EtOAc (10 ml/60 ml) three times. The organic layers were combined, dried, concentrated, and chromatographed on silica gel using gradient eluant of 0-50% methanol in dichloromethane to give the desired compound as pale solid (114 mg, 14%). MS (ESI) m/e [M+1]+478.

Workup

  1. customThen the reaction was quenched by water (20 mL)
  2. extractionThe mixture was extracted with THF/EtOAc (10 ml/60 ml) three times
  3. customdried
  4. concentrationconcentrated
  5. customchromatographed on silica gel using gradient eluant of 0-50% methanol in dichloromethane

Sources & evidence

ORD record
ord-cb9f41bc63fd4b5fa163e2f9d884b0e2
Source dataset
uspto-grants-2016_05
Patent number
US09328111B2

Reaction notes

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