1-Chloro-4-iodobenzene → HCID 131729465, compound

HRID 1644264Notes

Reaction equation

HRID 1644264 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([C@@H:9]1[C:18](=[O:19])[C:17]3[C:12]4=[C:13]([NH:20][N:21]=[C:11]4[CH2:10]1)[CH:14]=[N:15][CH:16]=3)[CH2:2]2.[Cl:22][C:23]1[CH:28]=[CH:27][C:26](I)=[CH:25][CH:24]=1.CN(C)C1CCCCC1N.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.C1(C)C=CC=CC=1>[ClH:22].[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([N:20]2[C:13]3[CH:14]=[N:15][CH:16]=[C:17]4[C:18](=[O:19])[C@@H:9]([CH:3]5[CH:4]6[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]6)[CH2:2]5)[CH2:10][C:11]([C:12]=34)=[N:21]2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 125101-Chloro-4-iodobenzeneHCID 62657Potassium Phosphate, TribasicHCID 12447266N1,N1-dimethylcyclohexane-1,2-diamineHCID 178515171HCID 178515171, compound

Product 1

HCID 131729465HCID 131729465, compoundYield 2.8%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (R)-7-(quinuclidin-3-yl)-7,8-dihydropyrazolo[3,4,5-de]isoquinolin-6(2H)-one (100 mg, 0.35 mmol) from Step C of Example 16, 1-chloro-4-iodobenzene (100 mg, 0.42 mmol), copper (I) iodide (3.3 mg, 0.02 mmol), N,N-dimethylcyclohexane-1,2-diamine (11 μL, 0.07 mmol), potassium phosphate tribasic (144 mg, 0.74 mmol) and toluene (1 ml) was placed in a sealed tube and degassed with nitrogen for 2 min. The reaction was heated at 110° C. for 24 h and, after cooling the solution to room temperature, the solvent was evaporated and the residue was purified by preparative TLC (silica gel, 90:10:1 dichloromethane/methanol/concentrated ammonium hydroxide) and preparative HPLC. The resultant compound was then treated with 1.25 M HCl in methanol to afford (R)-2-(4-chlorophenyl)-7-(quinuclidin-3-yl)-7,8-dihydropyrazolo[3,4,5-de]isoquinolin-6(2H)-one, hydrochloride salt (2.5 mg, 2%) as a light yellow solid. 1H NMR (500 MHz, D2O) δ 7.52 (d, J=8.5 Hz, 1H), 7.44 (dd, J=8.5, 7.0 Hz, 1H), 7.37 (d, J=7.0 Hz, 1H), 7.20-7.15 (m, 4H), 4.95 (d, J=17.5 Hz, 1H), 4.80 (d, J=18.0 Hz, 1H), 4.65-4.58 (m, 1H), 3.78 (t, J=10.5 Hz, 1H), 3.49-3.43 (m, 2H), 3.33-3.25 (m, 3H), 2.45 (s, 1H), 2.20-2.15 (m, 1H), 2.04-1.94 (m, 3H); MS (ESI+) m/z 393 (M+H); HPLC 98.4% (AUC), tR 15.66 min.

Workup

  1. customwas placed in a sealed tube
  2. customdegassed with nitrogen for 2 min
  3. temperatureafter cooling the solution to room temperature
  4. customthe solvent was evaporated
  5. customthe residue was purified by preparative TLC (silica gel, 90:10:1 dichloromethane/methanol/concentrated ammonium hydroxide) and preparative HPLC
  6. additionThe resultant compound was then treated with 1.25 M HCl in methanol

Sources & evidence

ORD record
ord-5bb75f859df348fbb6f5c4e663d3b4c3
Source dataset
uspto-grants-2012_02
Patent number
US08124600B2

Reaction notes

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