Phenylhydrazine → HCID 46182725, compound

HRID 1429862Notes

Reaction equation

HRID 1429862 reaction equation
[C:1]1([NH:7][NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O=C(CC(OC)=O)CC(OC)=O.C(OC(OCC)(OCC)C)C.NCC1C=NC=CC=1.[CH3:40][C:41]1[N:42]([CH2:70][C:71]2[CH:72]=[N:73][CH:74]=[CH:75][CH:76]=2)[C:43](=[O:69])[CH:44]=[C:45]2N(C(=O)CCCOC3C=CC=CC=3)N(C3C=CC=CC=3)[C:47](=[O:68])[C:46]=12.C(N(CC)CC)(C)C.[CH3:85][O:86][C:87]1[CH:88]=[C:89]([CH2:93][C:94](Cl)=[O:95])[CH:90]=[CH:91][CH:92]=1>CN(C=O)C>[CH3:85][O:86][C:87]1[CH:88]=[C:89]([CH2:93][C:94]([N:8]2[C:45]3[C:46](=[C:41]([CH3:40])[N:42]([CH2:70][C:71]4[CH:72]=[N:73][CH:74]=[CH:75][CH:76]=4)[C:43](=[O:69])[CH:44]=3)[C:47](=[O:68])[N:7]2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:95])[CH:90]=[CH:91][CH:92]=1

Participants

9

Reactant 7

HCID 7516PhenylhydrazineHCID 310183-PyridinemethanamineHCID 66221Triethyl orthoacetateHCID 74591Dimethyl 3-oxoglutarateHCID 521913N,N-Diethyl-2-propanamine2×HCID 27332463-Methoxyphenylacetyl chlorideHCID 45110928HCID 45110928, compound

Product 1

HCID 46182725HCID 46182725, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Following the general methods as outlined in Example 7, starting from phenylhydrazine, dimethyl 3-oxopentanedioate, 1,1,1-triethoxyethane, 3-aminomethylpyridine and acylation of the corresponding intermediate compound according to Formula (Ia) the following procedure was used: to a solution of 4-methyl-1-(4-phenoxybutanoyl)-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione (4) (Compound Ib, Scheme 1) (0.100 g, 0.301 mmol, 1 equiv.) in 3.2 mL of DMF was added dropwise iPrNEt2 (0.058 mL, 0.331 mmol, 1.1 equiv.) at 0° C. under a N2 atmosphere. The resulting mixture was stirred at 0° C. to give a red solution that was treated with 3-methoxyphenyl-acetyl chloride (0.061 g, 0.331 mmol, 1.1 equiv.) and allowed to come back to rt. After 30 min at rt, iPrNEt2 (0.058 mL, 0.331 mmol, 1.1 equiv.) was added and the reaction mixture was partitioned into EtOAc/water. Extractive workup was followed by drying of the organic phase over Na2SO4 and concentration in vacuo. The resulting residue was purified by flash chromatography over SiO2 (CH2Cl2:MeOH, 97:3) to give the titled compound as a beige solid (0.077 g, 53% yield). 1H NMR (500 MHz, CDCl3) 2.79 (s, 3H), 3.74 (s, 3H), 5.40 (s, 2H), 6.52 (s, 1H), 6.56 (d, J 7.6 Hz, 1H), 6.77 (dd, J 8.2, 1.6 Hz, 1H), 7.16 (m, 2H), 7.28 (m, 1H), 7.34 (m, 1H), 7.50-7.45 (m, 4H), 7.57 (d, J=7.9 Hz, 1H), 8.55 (m, 2H); MS (ESI+): 481.6; MS (ESI−): 479.3.

Workup

  1. customto give a red solution that
  2. customto come back to rt
  3. customthe reaction mixture was partitioned into EtOAc/water
  4. dry with materialby drying of the organic phase over Na2SO4 and concentration in vacuo
  5. customThe resulting residue was purified by flash chromatography over SiO2 (CH2Cl2:MeOH, 97:3)

Sources & evidence

ORD record
ord-862c6510b8934b76811b34d3b94784eb
Source dataset
uspto-grants-2015_01
Patent number
US08940760B2

Reaction notes

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