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

HRID 2173070Notes

Reaction equation

HRID 2173070 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]([CH:27]4[CH2:29][CH2:28]4)[CH:23]=3)[C:19]3[C:30](=[O:40])[N:31](C(OC(C)(C)C)=O)[CH2:32][C:18]=3[C:17]=2[F:41])[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]([CH:27]4[CH2:29][CH2:28]4)[CH:23]=3)[C:19]3[C:30](=[O:40])[NH:31][CH2:32][C:18]=3[C:17]=2[F:41])[CH2:13][CH2:12][O:11][CH2:10]1

Participants

5

Reactant 3

HCID 702EthanolHCID 204431481,4-Dioxane hydrochlorideHCID 71144066HCID 71144066, compound

Product 1

HCID 711438946-((3R,4R)-3-Aminotetrahydro-2H-pyran-4-ylamino)-4-(3-cyclopropylisothiazol-5-yl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-oneYield 68%

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-cyclopropylisothiazol-5-yl)-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (58.9 mg, 0.100 mmol) in MeOH (2.0 mL) was added 4N HCl/dioxane (2.0 mL, 8.00 mmol). The reaction 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 (26.5 mg, 62%). 1H NMR (500 MHz, DMSO-d6) δ ppm 0.82-0.92 (m, 2H), 0.95-1.06 (m, 2H), 1.70-1.85 (m, 1H), 2.07-2.17 (m, 1H), 2.18-2.26 (m, 1H), 3.56-3.66 (m, 1H), 3.72-3.84 (m, 2H), 3.95-4.08 (m, 2H), 4.26-4.36 (m, 1H), 4.41-4.53 (m, 2H), 7.46 (d, J=4.88 Hz, 1H), 8.02 (br s, 3H), 8.68 (s, 1H), 8.72 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C18H20FN5O2S, 390. found, 390.

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-2315db5cd599482fac117d7ae66c479f
Source dataset
uspto-grants-2015_06
Patent number
US09056873B2

Reaction notes

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