Acetic Acid → HCID 178457985, compound

HRID 521422Notes

Reaction equation

HRID 521422 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:35])([CH3:34])[C:13]([N:15]1[CH2:24][C:23]2[NH:22][C:21]3[CH:25]=[CH:26][CH:27]=[C:28]([C:29]([O:31]C)=O)[C:20]=3[C:19](=O)[C:18]=2[CH2:17][CH2:16]1)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[NH2:37][NH2:38].C(O)(=O)C.O>CC(N(C)C)=O.CCOC(C)=O>[CH3:34][C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH3:35])[C:13](=[O:14])[N:15]1[CH2:24][C:23]2[NH:22][C:21]3[CH:25]=[CH:26][CH:27]=[C:28]4[C:29](=[O:31])[NH:37][N:38]=[C:19]([C:20]=34)[C:18]=2[CH2:17][CH2:16]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 24654Hydrazine hydrate (1:1)HCID 89657465Methyl 2-(2-(((benzyloxy)carbonyl)amino)-2-methylpropanoyl)-5-oxo-1,2,3,4,5,10-hexahydrobenzo[b][1,7]naphthyridine-6-carboxylate

Product 1

HCID 178457985HCID 178457985, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
130 °C

Procedure

A solution of methyl 2-(2-(((benzyloxy)carbonyl)amino)-2-methylpropanoyl)-5-oxo-1,2,3,4,5,10-hexahydrobenzo[b][1,7]naphthyridine-6-carboxylate (0.11 g) and hydrazine hydrate (1.0 mL) in DMA (1.5 mL) was heated at 130° C. for 1.5 h, acetic acid (2.0 mL) was added and the mixture was stirred at 130° C. for another 12 hours. The reaction mixture was cooled to room temperature, then water (15 mL) and EtOAc (50 mL) were added. The organic phase was separated and then washed with aqueous NaHCO3 (2×10 ml) and brine (20 ml), dried over Na2SO4, filtered, the organic phase was concentrated in vacuum to give the crude product, which was purified by Pre-HPLC to afford benzyl (2-methyl-1-oxo-1-(3-oxo-10,11-dihydro-2H-phthalazino[8,1-bc][1,7]naphthyridin-9(3H,7H,8H)-yl)propan-2-yl)carbamate (46 mg, 42%) as a yellow solid. 1H NMR (DMSO-d6) δ 11.8 (s, 1H), 10.6 (s, 1H), 8.4 (s, 1H), 7.65 (t, 1H, J=7.8 Hz), 7.49 (d, 1H, J=7.8 Hz), 7.25-7.35 (m, 6H), 4.90-4.91 (m, 2H), 4.34-4.40 (m, 2H), 3.83-3.89 (m 2H), 2.32-2.34 (m, 2H), and 1.40 (s, 6H). MS (ESI) m/e [M+1]+460.0.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic phase was separated
  3. washwashed with aqueous NaHCO3 (2×10 ml) and brine (20 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe organic phase was concentrated in vacuum
  7. customto give the crude product, which
  8. customwas purified by Pre-HPLC

Sources & evidence

ORD record
ord-4507d69beaa843e3bf4185f4e52e0f16
Source dataset
uspto-grants-2016_05
Patent number
US09328111B2

Reaction notes

Loading…