Potassium Carbonate → 2-Chloro-4,4-difluoro-1'-[[1-(3-methoxy-2-pyridyl)-3-methyl-pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]

HRID 1517609Notes

Reaction equation

HRID 1517609 reaction equation
[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:20][CH2:21][C:22]([F:24])([F:23])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:19])=[N:16][NH:17][CH:18]=1)[CH2:9][CH2:8]3.C(=O)([O-])[O-].[K+].[K+].I[C:32]1[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[CH:34][N:33]=1.CN[C@@H]1CCCC[C@H]1NC>[Cu]I.C1(C)C=CC=CC=1>[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:20][CH2:21][C:22]([F:23])([F:24])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:19])=[N:16][N:17]([C:32]2[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[CH:34][N:33]=2)[CH:18]=1)[CH2:9][CH2:8]3

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 8171732-Iodo-3-methoxypyridineHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 178434546HCID 178434546, compound

Product 1

HCID 582686102-Chloro-4,4-difluoro-1'-[[1-(3-methoxy-2-pyridyl)-3-methyl-pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]Yield 54.1%

Reagents, catalysts & solvents 2

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

Procedure

To a screw-cap test tube are added copper(I) iodide (23.74 mg, 0.125 mmol), 2-chloro-4,4-difluoro-1′-[(3-methyl-1H-pyrazol-4-yl)methyl]spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine] (233.00 mg, 0.623 mmol), potassium carbonate (182.71 mg, 1.31 mmol), toluene (2 mL) (previously bubbled with nitrogen for 20 min) and a stir bar. The reaction mixture is bubbled with nitrogen for 20 minutes and then 2-iodo-3-methoxypyridine (302.01 mg, 1.25 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (39.31 mL, 0.25 mmol) are added. The reaction tube is quickly sealed (caution: build-up of pressure possible; use a safety shield) and immersed in a preheated oil bath at 110° C. for 24 hours with the aid of a magnetic stirrer. Then, the mixture is poured on SCX column (25 g) and eluted with methanol and then 2N solution of ammonia in methanol. The basic fraction is concentrated and the resulting residue is purified by basic-HPLC to give 162 mg of the title compound. MS (m/z): 481 (M+1).

Workup

  1. custompreviously bubbled with nitrogen for 20 min) and a stir bar
  2. customThe reaction mixture is bubbled with nitrogen for 20 minutes
  3. customThe reaction tube is quickly sealed (caution
  4. additionThen, the mixture is poured on SCX column (25 g)
  5. washeluted with methanol
  6. concentrationThe basic fraction is concentrated
  7. customthe resulting residue is purified by basic-HPLC

Sources & evidence

ORD record
ord-25627668f3ed4a23adb05f91132f636d
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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