Sodium Thiosulfate → 5-fluoro-1-(piperazin-1-ylmethyl)-2,3-dihydro-1H-indene-4-carbonitrile

HRID 2173248Notes

Reaction equation

HRID 2173248 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]2[CH:7]([CH2:11]O)[CH2:6][CH2:5][C:4]=2[C:3]=1[C:13]#[N:14].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O.[O-]S([O-])(=S)=O.[Na+].[Na+].C([N:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1)(OC(C)(C)C)=O.C([BH3-])#N.[Na+]>C(Cl)Cl.CC(O)=O>[F:1][C:2]1[CH:10]=[CH:9][C:8]2[CH:7]([CH2:11][N:51]3[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]3)[CH2:6][CH2:5][C:4]=2[C:3]=1[C:13]#[N:14]

Participants

8

Reactant 5

HCID 24477Sodium ThiosulfateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 159087TriacetoxyperiodinaneHCID 5003444Sodium cyanoborohydrideHCID 666463905-fluoro-1-(hydroxymethyl)-2,3-dihydro-1H-indene-4-carbonitrile

Product 1

HCID 595686755-fluoro-1-(piperazin-1-ylmethyl)-2,3-dihydro-1H-indene-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 5-Fluoro-1-(hydroxymethyl)-2,3-dihydro-1H-indene-4-carbonitrile (20 mg, 0.105 mmol) in DCM was treated with Dess-MartinPeriodinane (89 mg, 0.209 mmol) in DCM. When TLC showed the reaction was done, Na2S2O3 was added to the reaction. The solution was stirred vigorously until the two layers turned clear. The mixture was extracted with DCM, and the DCM layer was washed with Na2CO3 and brine, dried over sodium sulfate, and concentrated. The resulting oil was then treated with N-Boc-piperazine (39.0 mg, 0.209 mmol) and Sodium Cyanoborohydride (33 mg, 0.52 mmol) in DCM with a few drops of HOAc. LC showed complete reaction within 6 hours. The reductive amination adduct was then purified by MPLC. Finally, the Boc group was removed by treating the carbamate with 4N HCl in dioxane. After removal of solvent, the title material was obtained. LC-MS (IE, m/z): 260 [M+1]+.

Workup

  1. extractionThe mixture was extracted with DCM
  2. washthe DCM layer was washed with Na2CO3 and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customreaction within 6 hours
  6. customThe reductive amination adduct was then purified by MPLC
  7. customFinally, the Boc group was removed
  8. additionby treating the carbamate with 4N HCl in dioxane
  9. customAfter removal of solvent

Sources & evidence

ORD record
ord-9663b0f686b247068322e49d3e55e2fa
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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