Ethanol → 6-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(isothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 2173066Notes

Reaction equation

HRID 2173066 reaction equation
C(OC([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[S:26][N:25]=[CH:24][CH:23]=3)[C:19]3[C:27](=[O:37])[N:28](C(OC(C)(C)C)=O)[CH2:29][C:18]=3[C:17]=2[F:38])[CH2:13][CH2:12][O:11][CH2:10]1)=O)(C)(C)C.Cl.O1CCOCC1.CCO>CO>[NH2:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[S:26][N:25]=[CH:24][CH:23]=3)[C:19]3[C:27](=[O:37])[NH:28][CH2:29][C:18]=3[C:17]=2[F:38])[CH2:13][CH2:12][O:11][CH2:10]1

Participants

5

Reactant 3

HCID 702EthanolHCID 204431481,4-Dioxane hydrochlorideHCID 71143875HCID 71143875, compound

Product 1

HCID 711441386-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(isothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneYield 63.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-7-fluoro-4-(isothiazol-5-yl)-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (65.8 mg, 0.120 mmol) in MeOH (1.0 mL) was added 4N HCl/dioxane (1.0 mL, 4.00 mmol). The reaction mixture was heated to 60° C. for 1 hour and was subsequently concentrated in vacuo. The residue was triturated with EtOAc and filtered. The filter cake was washed with EtOAc to give a yellow solid, which was suspended into EtOH. The mixture was stirred at 80° C. for 30 minutes and allowed to cool to room temperature. The resulting precipitate was collected by filtration and washed with EtOH to give a hydrochloride salt of the title compound as an off-white solid (26.5 mg, 57%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.74-1.85 (m, 1H), 2.08-2.23 (m, 1H), 3.56-3.68 (m, 1H), 3.80 (d, J=11.23 Hz, 2H), 3.96-4.11 (m, 2H), 4.29-4.39 (m, 1H), 4.42-4.55 (m, 2H), 7.49 (d, J=5.37 Hz, 1H), 8.08 (br s, 3H), 8.63 (s, 1H), 8.71 (s, 1H), 8.96 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C15H16FN5O2S, 350. found, 350.

Workup

  1. concentrationwas subsequently concentrated in vacuo
  2. customThe residue was triturated with EtOAc
  3. filtrationfiltered
  4. washThe filter cake was washed with EtOAc
  5. customto give a yellow solid, which
  6. temperatureto cool to room temperature
  7. filtrationThe resulting precipitate was collected by filtration
  8. washwashed with EtOH

Sources & evidence

ORD record
ord-7cac348a8b2d4085836d1b9f20f66625
Source dataset
uspto-grants-2015_06
Patent number
US09056873B2

Reaction notes

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