Potassium Carbonate → HCID 71164906, compound

HRID 2173107Notes

Reaction equation

HRID 2173107 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20](Cl)[C:19]2[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=2[C:17]=1[F:34])=[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[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([C:44]2[CH:43]=[N:42][N:39]3[CH:40]=[CH:41][C:36]([CH3:35])=[CH:37][C:38]=23)[C:19]2[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=2[C:17]=1[F:34])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 12035N-Acetyl-L-CysteineHCID 71143934HCID 71143934, compoundHCID 86654740tert-Butyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

Product 1

HCID 71164906HCID 71164906, compoundYield 46.1%

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-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (200 mg, 0.401 mmol) and 5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine (124 mg, 0.481 mmol), followed by potassium carbonate (325 mesh powder) (111 mg, 0.802 mmol), DMA (6 mL), and water (0.400 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 (10.93 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 (65.4 mg, 0.401 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 55-80% 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 (110 mg, 46%).

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 55-80% 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-a5ab81e744f0410f81d0b7036758fb40
Source dataset
uspto-grants-2015_06
Patent number
US09056873B2

Reaction notes

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