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

HRID 2173062Notes

Reaction equation

HRID 2173062 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]=[C:24]([CH2:27][CH3:28])[CH:23]=3)[C:19]3[C:29](=[O:39])[N:30](C(OC(C)(C)C)=O)[CH2:31][C:18]=3[C:17]=2[F:40])[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]=[C:24]([CH2:27][CH3:28])[CH:23]=3)[C:19]3[C:29](=[O:39])[NH:30][CH2:31][C:18]=3[C:17]=2[F:40])[CH2:13][CH2:12][O:11][CH2:10]1

Participants

5

Reactant 3

HCID 702EthanolHCID 204431481,4-Dioxane hydrochlorideHCID 71164899tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-(3-ethylisothiazol-5-yl)-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

Product 1

HCID 711439356-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(3-ethylisothiazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneYield 77.2%

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)-4-(3-ethylisothiazol-5-yl)-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (53 mg, 0.092 mmol) in MeOH (10 mL) was added 4N HCl/dioxane (10.0 mL, 40.0 mmol). The mixture was heated to 60° C. for 1 hour and then 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 then cooled 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 (26.8 mg, 70%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.26 (t, J=7.57 Hz, 3H), 1.74-1.83 (m, 1H), 2.07-2.20 (m, 1H), 2.81 (q, J=7.60 Hz, 2H), 3.57-3.67 (m, 1H), 3.73-3.84 (m, 2H), 3.96-4.09 (m, 2H), 4.28-4.36 (m, 1H), 4.43-4.53 (m, 2H), 7.46 (d, J=5.37 Hz, 1H), 8.05 (br s, 3H), 8.68 (s, 1H), 8.80 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C17H20FN5O2S, 378. found, 378.

Workup

  1. concentrationconcentrated 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. temperaturecooled to room temperature
  7. filtrationThe resulting precipitate was collected by filtration
  8. washwashed with EtOH

Sources & evidence

ORD record
ord-fc3d2f9634564e538eabc479fb3fcf47
Source dataset
uspto-grants-2015_06
Patent number
US09056873B2

Reaction notes

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