Methanol → HCID 131731377, compound

HRID 1020882Notes

Reaction equation

HRID 1020882 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]1[CH2:13][CH:12]([N:14]2[CH2:21][C:20]3[C:16](=[N:17][N:18]([S:22]([CH3:25])(=[O:24])=[O:23])[CH:19]=3)[CH2:15]2)[C:11](=O)[NH:10][C@@H:9]1[C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[F:34])([CH3:4])([CH3:3])[CH3:2].CO>O1CCCC1>[C:1]([O:5][C:6](=[O:35])[NH:7][C@H:8]1[CH2:13][C@@H:12]([N:14]2[CH2:21][C:20]3[C:16](=[N:17][N:18]([S:22]([CH3:25])(=[O:23])=[O:24])[CH:19]=3)[CH2:15]2)[CH2:11][NH:10][C@@H:9]1[C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[F:34])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 887MethanolHCID 131731378HCID 131731378, compound

Product 1

HCID 131731377HCID 131731377, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of the product from Step D (18.43 g, 36.0 mmol) in tetrahydrofuran (250 mL) was added borane dimethyl sulfide complex solution (144 mL, 288 mmol, 2.0 M solution in tetrahydrofuran) over 15 min. The reaction was placed in a preheated 70° C. bath and stirred for 75 min. The mixture was cooled to 0° C. and methanol (100 mL) slowly added over 15 min. The ice bath was removed and the mixture stirred for 30 min and the solvent removed in vacuo. The residue was dissolved in ethanol (150 mL) and heated at 70° C. for 4 h, cooled to ambient temperature and the solvent removed in vacuo. The crude solid was purified by column chromatography (silica gel Biotage 40M) eluting with methanol/ethyl acetate (gradient from 0% to 10%) to give the minor (first eluting) diastereomer tert-butyl {(2R,3S,5S)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]piperidin-3-yl}carbamate and the major (second eluting) diastereomer, the title compound as colorless solids. LC/MS 498.2 (M+1).

Workup

  1. customwas placed in a preheated 70° C.
  2. customThe ice bath was removed
  3. stirringthe mixture stirred for 30 min
  4. customthe solvent removed in vacuo
  5. dissolutionThe residue was dissolved in ethanol (150 mL)
  6. temperatureheated at 70° C. for 4 h
  7. temperaturecooled to ambient temperature
  8. customthe solvent removed in vacuo
  9. customThe crude solid was purified by column chromatography (silica gel Biotage 40M)
  10. washeluting with methanol/ethyl acetate (gradient from 0% to 10%)
  11. customto give
  12. washthe minor (first eluting) diastereomer tert-butyl {(2R,3S,5S)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]piperidin-3-yl}carbamate
  13. washthe major (second eluting) diastereomer

Sources & evidence

ORD record
ord-7eda6c956c3f45c1b1ca51b0eb25b1f6
Source dataset
uspto-grants-2014_05
Patent number
US08716482B2

Reaction notes

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