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

HRID 1517606Notes

Reaction equation

HRID 1517606 reaction equation
[Cl:1][C:2]1[S:32][C:5]2[C:6]3([CH2:16][CH2:15][N:14]([CH2:17][C:18]4[C:19]([CH3:31])=[N:20][N:21]([C:23]5[N:30]=[CH:29][CH:28]=[CH:27][C:24]=5[CH:25]=[O:26])[CH:22]=4)[CH2:13][CH2:12]3)[O:7][CH2:8][C:9]([F:11])([F:10])[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC(S([CH2:48][N+:49]#[C-:50])(=O)=O)=CC=1>CO>[Cl:1][C:2]1[S:32][C:5]2[C:6]3([CH2:12][CH2:13][N:14]([CH2:17][C:18]4[C:19]([CH3:31])=[N:20][N:21]([C:23]5[C:24]([C:25]6[O:26][CH:50]=[N:49][CH:48]=6)=[CH:27][CH:28]=[CH:29][N:30]=5)[CH:22]=4)[CH2:15][CH2:16]3)[O:7][CH2:8][C:9]([F:11])([F:10])[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 161915Tosylmethyl isocyanideHCID 582685962-[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde

Product 1

HCID 582686355-(2-(4-((2'-Chloro-4',4'-difluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)methyl)-3-methyl-1H-pyrazol-1-yl)pyridin-3-yl)oxazoleYield 71.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
65 °C

Procedure

To a screw-cap test tube containing 2-(4-((2′-chloro-4′,4′-difluoro-4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-yl)methyl)-3-methyl-1H-pyrazol-1-yl)nicotinaldehyde (0.120 g, 0.25 mmol) in methanol (2.5 mL) are added potassium carbonate (0.104 g, 0.75 mmol) and p-toluenesulfonylmethyl isocyanide (0.054 g, 0.28 mmol) under nitrogen. The reaction tube is quickly sealed (caution: build-up of pressure possible; use a safety shield) and is stirred in a preheated oil bath at 65° C. for 3 hr. with the aid of a magnetic stirrer. The mixture is diluted with methanol and purified using a 2 g SCX cartridge. The solvent is evaporated in vacuo. The resulting residue is purified by normal phase Isco chromatography eluting with hexane/ethanol (5-30%) to give 0.093 g of the title compound. MS (m/z): 518 (M+1)

Workup

  1. customThe reaction tube is quickly sealed (caution
  2. custompurified
  3. customThe solvent is evaporated in vacuo
  4. customThe resulting residue is purified by normal phase Isco chromatography
  5. washeluting with hexane/ethanol (5-30%)

Sources & evidence

ORD record
ord-e6555a125dba4eac8fa5c2c0007f921f
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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