Sodium triacetoxyborohydride → 2-chloro-4,4-difluoro-1'-[[1-(3-fluoro-2-pyridyl)-3-(isopropoxymethyl)pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]

HRID 1517607Notes

Reaction equation

HRID 1517607 reaction equation
[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:13][CH2:14][C:15]([F:17])([F:16])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]3.[F:18][C:19]1[C:20]([N:25]2[CH:29]=[C:28]([CH:30]=O)[C:27]([CH2:32][O:33][CH:34]([CH3:36])[CH3:35])=[N:26]2)=[N:21][CH:22]=[CH:23][CH:24]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:13][CH2:14][C:15]([F:16])([F:17])[C:4]=2[CH:3]=1)[CH2:8][CH2:9][N:10]([CH2:30][C:28]1[C:27]([CH2:32][O:33][CH:34]([CH3:36])[CH3:35])=[N:26][N:25]([C:20]2[C:19]([F:18])=[CH:24][CH:23]=[CH:22][N:21]=2)[CH:29]=1)[CH2:11][CH2:12]3

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 582685841-(3-Fluoro-2-pyridyl)-3-(isopropoxymethyl)pyrazole-4-carbaldehydeHCID 582685982'-Chloro-4',4'-difluoro-4',5'-dihydrospiro[piperidine-4,7'-[7H]thieno[2,3-c]pyran]

Product 1

HCID 582685642-chloro-4,4-difluoro-1'-[[1-(3-fluoro-2-pyridyl)-3-(isopropoxymethyl)pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]Yield 21.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine] (170 mg, 0.61 mmol) in dichloromethane (2.4 mL), 1-(3-fluoro-2-pyridyl)-3-(isopropoxymethyl)pyrazole-4-carbaldehyde (192 mg) is added. The mixture is stirred 10 min at room temperature. Then, sodium triacetoxyborohydride (268.3 mg) is added, and the reaction is stirred at room temperature overnight. The mixture is diluted with dichloromethane and quenched slowly with sodium bicarbonate (saturated solution). The organic phase is then extracted with more dichloromethane, decanted, dried over magnesium sulfate and solvent evaporated under reduced pressure. The residue is purified by reverse phase HPLC to give 67.9 mg of 2-chloro-4,4-difluoro-1′-[[1-(3-fluoro-2-pyridyl)-3-(isopropoxymethyl)pyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]. MS (m/z): 527 (M+1).

Workup

  1. stirringthe reaction is stirred at room temperature overnight
  2. customquenched slowly with sodium bicarbonate (saturated solution)
  3. extractionThe organic phase is then extracted with more dichloromethane
  4. customdecanted
  5. dry with materialdried over magnesium sulfate and solvent
  6. customevaporated under reduced pressure
  7. customThe residue is purified by reverse phase HPLC

Sources & evidence

ORD record
ord-7f80fceaeaf249e197eb42bc44eb4437
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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