Dichloromethane → ethyl 4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(3-fluoro-2-pyridyl)pyrazole-3-carboxylate

HRID 1517616Notes

Reaction equation

HRID 1517616 reaction equation
[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:24][CH2:25][C:26]([F:28])([F:27])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N:16][NH:17][CH:18]=1)[CH2:9][CH2:8]3.C(=O)([O-])[O-].[K+].[K+].F[C:36]1[C:41]([F:42])=[CH:40][CH:39]=[CH:38][N:37]=1.C(Cl)Cl>CN(C)C=O>[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:24][CH2:25][C:26]([F:27])([F:28])[C:4]=2[CH:3]=1)[CH2:8][CH2:9][N:10]([CH2:13][C:14]1[C:15]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N:16][N:17]([C:36]2[C:41]([F:42])=[CH:40][CH:39]=[CH:38][N:37]=2)[CH:18]=1)[CH2:11][CH2:12]3

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27831762,3-DifluoropyridineHCID 178470489HCID 178470489, compound

Product 1

HCID 58268607ethyl 4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(3-fluoro-2-pyridyl)pyrazole-3-carboxylateYield 65.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-1H-pyrazole-3-carboxylate (22.5 g, 52.10 mmoles) in Dimethylformamide (225.00 mL) is added Potassium Carbonate (10.80 g, 78.14 mmoles) and 2,3-difluoropyridine (7.19 g, 62.52 mmoles) and the resulting suspension is stirred at 60° C. 15 h. Then, reaction mixture is poured over Ice/brine (30 mL) and CH2Cl2 (50 mL) is added to the resulting suspension. Solution is washed with H2O (2×50 mL). Organics are dried over sodium sulfate and concentrated to give a crude which is purified via SiO2 filtration eluting with 2-propanol/CH2Cl2 mixtures to give 18 g of the title compound. MS (m/z): 527 (M+1).

Workup

  1. custom15 h
  2. customThen, reaction mixture
  3. additionis added to the resulting suspension
  4. washSolution is washed with H2O (2×50 mL)
  5. dry with materialOrganics are dried over sodium sulfate
  6. concentrationconcentrated
  7. customto give a crude which
  8. filtrationis purified via SiO2 filtration
  9. washeluting with 2-propanol/CH2Cl2

Sources & evidence

ORD record
ord-c2a571a68419468d91d8cdef6dba6ac9
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

Loading…