Phosphorus oxide (P4O10) → HCID 86613800, compound

HRID 2378123Notes

Reaction equation

HRID 2378123 reaction equation
[CH:1]([O:4][C:5]([N:7]1[C:16]2[C:11](=[N:12][C:13]([C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=2)[C@H:10]([N:21]([CH2:28][C:29]2[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[C:31]([C:39]([F:42])([F:41])[F:40])[CH:30]=2)[C:22](=O)[CH2:23][C:24](=O)[CH3:25])[CH2:9][C@@H:8]1[CH2:43][CH3:44])=[O:6])([CH3:3])[CH3:2].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.O.[NH2:60][NH2:61]>CCO>[CH:1]([O:4][C:5]([N:7]1[C:16]2[C:11](=[N:12][C:13]([C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=2)[C@H:10]([N:21]([CH2:28][C:29]2[CH:34]=[C:33]([C:35]([F:36])([F:37])[F:38])[CH:32]=[C:31]([C:39]([F:42])([F:41])[F:40])[CH:30]=2)[C:22]2[CH:23]=[C:24]([CH3:25])[NH:61][N:60]=2)[CH2:9][C@@H:8]1[CH2:43][CH3:44])=[O:6])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 14812Phosphorus oxide (P4O10)HCID 24654Hydrazine hydrate (1:1)HCID 86613801HCID 86613801, compound

Product 1

HCID 86613800HCID 86613800, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

Add slowly cold (ice bath) absolute EtOH (1.7 mL) to a cooled 0° C. stirred mixture of (+/−)-cis-4-[(3,5-bis-trifluoromethyl-benzyl)-(3-oxo-butyryl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid isopropyl ester (221 mg, 0.34 mmol) and phosphorus pentoxide (880 mg, 6.2 mmol). Add hydrazine hydrate (0.105 mL, 3.4 mmol) while keeping the mixture cooled at 0° C. Seal the tube and heat the reaction mixture at 100° C. overnight. Cool down the mixture and remove the solvents under reduced pressure. Partition the residue between water and dichloromethane. Separate the layers and dry the organic phase, filter, and concentrate in vacuo. Purify the residue by silica gel flash chromatography, eluting with hexanes/ethyl acetate, to afford the title compound (82 mg, 38%). MS (ES+): 638 (M+H).

Workup

  1. customSeal the tube
  2. temperatureheat the reaction mixture at 100° C. overnight
  3. temperatureCool down the mixture
  4. customremove the solvents under reduced pressure
  5. customPartition the residue between water and dichloromethane
  6. customSeparate the layers
  7. customdry the organic phase
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. customPurify the residue by silica gel flash chromatography
  11. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-e8c762f57f9a4fc39147658ff63e55b3
Source dataset
uspto-grants-2008_12
Patent number
US07470705B2

Reaction notes

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