(Dimethyl sulfide)trihydroboron → (R)-4-[6-(4-Methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-3-(2,2,2-trifluoro-ethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 2279160Notes

Reaction equation

HRID 2279160 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[C:17]3[C:34]([CH3:35])=[N:33][N:32]([CH:36]4[CH2:41][CH2:40][CH2:39][CH2:38][O:37]4)[C:18]=3[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][O:30][CH3:31])=[CH:24][CH:23]=3)[CH:21]=2)=O)[C@H:10]([CH2:42][C:43]([F:46])([F:45])[F:44])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B.CSC>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:16]2[CH:21]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][O:30][CH3:31])=[CH:24][CH:23]=3)[N:19]=[C:18]3[N:32]([CH:36]4[CH2:41][CH2:40][CH2:39][CH2:38][O:37]4)[N:33]=[C:34]([CH3:35])[C:17]=23)[C@H:10]([CH2:42][C:43]([F:44])([F:45])[F:46])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 12423031(Dimethyl sulfide)trihydroboronHCID 90013556(R)-4-[6-(4-Methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-3-(2,2,2-trifluoro-ethyl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 90013379(R)-4-[6-(4-Methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-ylmethyl]-3-(2,2,2-trifluoro-ethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 84.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 557 mg of (R)-4-[6-(4-Methoxymethoxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-3-(2,2,2-trifluoro-ethyl)-piperazine-1-carboxylic acid tert-butyl ester in 8 ml of dry THF 6.9 ml of borane-dimethylsulfide complex (1 M in DCM) was added slowly at r.t., and the reaction was heated to reflux for 3.5 h. The reaction was quenched by the addition of methanol, and the solvents were evaporated. The residue was purified by flash chromatography (silica, heptanes/ethyl acetate) yielding 460 mg (84%) of the title compound.

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 3.5 h
  3. customThe reaction was quenched by the addition of methanol
  4. customthe solvents were evaporated
  5. customThe residue was purified by flash chromatography (silica, heptanes/ethyl acetate)

Sources & evidence

ORD record
ord-1e71ff12210f4c779b7a9612afb062d4
Source dataset
uspto-grants-2015_09
Patent number
US09133181B2

Reaction notes

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