Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate → tert-Butyl (1S,2R)-2-(4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

HRID 515996Notes

Reaction equation

HRID 515996 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[CH:25]=[C:24]([C:26]#[N:27])[C:19]([C:20]([O:22]C)=O)=[C:18]([C:28]2[CH:29]=[N:30][N:31]([CH3:33])[CH:32]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].CO.CC(O)=O>[CH3:33][N:31]1[CH:32]=[C:28]([C:18]2[C:19]3[C:20](=[O:22])[NH:27][CH2:26][C:24]=3[CH:25]=[C:16]([NH:15][C@@H:10]3[CH2:11][CH2:12][CH2:13][CH2:14][C@@H:9]3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[N:17]=2)[CH:29]=[N:30]1

Participants

5

Reactant 1

HCID 67237740Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

Product 1

HCID 86654709tert-Butyl (1S,2R)-2-(4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamateYield 58.1%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A solution of methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate (110 mg, 0.242 mmol) and palladium on carbon (2.58 mg, 0.024 mmol) in MeOH (5 mL) and HOAc (1 mL) was stirred at RT overnight under H2 atmosphere. After reaction, the mixture was filtered through Celite, the filtrate was evaporated, and the residue was diluted with MeOH and sat aq NaHCO3. The mixture was stirred at RT for 30 min and extracted with EtOAc. The organic phase was washed with brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2 and preparative HPLC to give the title compound (60 mg, 58.1%). 1H NMR (500 MHz, CDCl3) δ ppm 1.26-1.87 (m, 17 H), 3.91 (s, 3 H), 4.25 (br s, 2 H), 5.16-5.49 (m 2 H), 6.23 (br s, 1 H), 6.75 (br s, 1 H), 8.18-8.44 (m, 1 H), 8.76-9.05 (m, 1 H).

Workup

  1. customAfter reaction
  2. filtrationthe mixture was filtered through Celite
  3. customthe filtrate was evaporated
  4. additionthe residue was diluted with MeOH
  5. extractionextracted with EtOAc
  6. washThe organic phase was washed with brine
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe residue was purified by chromatography on SiO2 and preparative HPLC

Sources & evidence

ORD record
ord-931f8e17ba6a437ca559b53a98ee6c5e
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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