tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-7-fluoro-3-oxo-4-(3-vinylisothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate → 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

HRID 2173061Notes

Reaction equation

HRID 2173061 reaction equation
[C:1]([O:5][C:6]([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]=[CH2:28])[CH:23]=3)[C:19]3[C:29](=[O:39])[N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:31][C:18]=3[C:17]=2[F:40])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([O:5][C:6]([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:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:31][C:18]=3[C:17]=2[F:40])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 1

HCID 86727256tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-7-fluoro-3-oxo-4-(3-vinylisothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

Product 1

HCID 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)-carboxylateYield 94.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-7-fluoro-3-oxo-4-(3-vinylisothiazol-5-yl)-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (58 mg, 0.101 mmol) in MeOH (1.0 mL) was added Pd/C (30 mg, 0.282 mmol) under N2 atmosphere. The mixture was stirred at room temperature overnight under H2 atmosphere. The solids were removed by filtration, and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (Flash 60 column) eluting with hexane/EtOAc (1:1) to give the title compound as a yellow solid (54.9 mg, 94%). 1H NMR (500 MHz, CDCl3) δ ppm 1.36 (t, J=7.57 Hz, 3H), 1.48 (br s, 9H), 1.61 (s, 9H), 1.71-1.82 (m, 1H), 2.20-2.33 (m, 1H), 2.91 (q, J=7.60 Hz, 2H), 3.64 (t, J=11.72 Hz, 1H), 3.74 (d, J=11.72 Hz, 1H), 3.91-3.99 (m, 1H), 4.01-4.10 (m, 2H), 4.23-4.34 (m, 1H), 4.72 (s, 2H), 5.37 (d, J=6.83 Hz, 1H), 6.47 (br s, 1H), 8.78 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C27H36FN5O6S, 578. found, 578.

Workup

  1. customThe solids were removed by filtration
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was purified by silica gel chromatography (Flash 60 column)
  4. washeluting with hexane/EtOAc (1:1)

Sources & evidence

ORD record
ord-911a42d8700e47c18a99a5116ba7e093
Source dataset
uspto-grants-2015_06
Patent number
US09056873B2

Reaction notes

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