Potassium Carbonate → HCID 71143864, compound

HRID 2173105Notes

Reaction equation

HRID 2173105 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](Cl)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:35][C:36]1[CH:41]=[CH:40][N:39]2[N:42]=[CH:43][C:44](B3OC(C)(C)C(C)(C)O3)=[C:38]2[CH:37]=1.C(=O)([O-])[O-].[K+].[K+].C(N[C@H](C(O)=O)CS)(=O)C>O.CC(N(C)C)=O>[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:44]3[CH:43]=[N:42][N:39]4[CH:40]=[CH:41][C:36]([CH3:35])=[CH:37][C:38]=34)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 12035N-Acetyl-L-CysteineHCID 71143934HCID 71143934, compoundHCID 86654748tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

Product 1

HCID 71143864HCID 71143864, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

To a 25 mL reaction flask equipped with magnetic stir bar and thermometer was added tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (200 mg, 0.399 mmol) and 5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine (124 mg, 0.479 mmol), followed by potassium carbonate (325 mesh powder) (110 mg, 0.798 mmol), DMA (10 mL), and water (0.667 mL). The mixture was stirred at room temperature for 3 min before degassing with vacuum and N2 back-fill (5×). To the resulting deep purple mixture was added Pd-118 (10.89 mg, 0.016 mmol). The reaction mixture was degassed again with vacuum and N2 back-fill (5×). The flask was wrapped tightly with plastic film, placed in an oil bath, and the reaction mixture was stirred at 80° C. for 18 hours. Solid N-acetyl cysteine (65.2 mg, 0.399 mmol) was added and the mixture was stirred at 70° C. for 2 h. The mixture was subsequently diluted with water and extracted with EtOAc (200 mL). The organic layer was dried and concentrated to give a residue, which was purified by preparative HPLC, eluting with a gradient of 45-70% ACN (0.035% TFA) and water (0.05% TFA). The fractions were collected to give, upon basic work-up, the title compound as a light yellow solid (50 mg, 21%).

Workup

  1. customTo a 25 mL reaction flask
  2. customequipped with magnetic stir bar
  3. custombefore degassing with vacuum and N2 back-fill (5×)
  4. customThe reaction mixture was degassed again with vacuum and N2 back-fill (5×)
  5. customplaced in an oil bath
  6. stirringthe reaction mixture was stirred at 80° C. for 18 hours
  7. stirringthe mixture was stirred at 70° C. for 2 h
  8. extractionextracted with EtOAc (200 mL)
  9. customThe organic layer was dried
  10. concentrationconcentrated
  11. customto give a residue, which
  12. customwas purified by preparative HPLC
  13. washeluting with a gradient of 45-70% ACN (0.035% TFA) and water (0.05% TFA)
  14. customThe fractions were collected
  15. customto give, upon basic work-up

Sources & evidence

ORD record
ord-7e0f155c6d6946ca955c4411889dfbc5
Source dataset
uspto-grants-2015_06
Patent number
US09056873B2

Reaction notes

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