Trifluoroacetic acid → HCID 53251176, compound

HRID 516132Notes

Reaction equation

HRID 516132 reaction equation
C(OC([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(OC(C)(C)C)=O)[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=O)(C)(C)C.[F:35][C:36]([F:43])([F:42])[C:37]1[N:38]=[CH:39][NH:40][CH:41]=1.C([O-])([O-])=O.[K+].[K+].[C:50]([OH:56])([C:52]([F:55])([F:54])[F:53])=[O:51]>C(#N)C>[C:50]([OH:56])([C:52]([F:55])([F:54])[F:53])=[O:51].[NH2:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([N:40]3[CH:41]=[C:37]([C:36]([F:43])([F:42])[F:35])[N:38]=[CH:39]3)[C:19]3[C:23](=[O:33])[NH:24][CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 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)-carboxylateHCID 178418921HCID 178418921, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 53251176HCID 53251176, compoundYield 8.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a 10 mL sealed cap glass vial, 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 (60 mg, 0.120 mmol), 4-(trifluoromethyl)-1H-imidazole (48.9 mg, 0.359 mmol) and K2CO3 (66.2 mg, 0.479 mmol) were dissolved in ACN (2 mL). The cap was sealed and the mixture was reacted at 100° C. for 16 h. The reaction mixture was subsequently filtered through a Buchner funnel to remove un-dissolved K2CO3. The solids were washed with ACN (2×5 mL) and the filtrate was evaporated to give a residue, which was treated with TFA (2 mL) at RT for 20 min to remove the protecting groups. Next, TFA was evaporated from the reaction mixture. The product was reconstituted in DMSO (5 mL) and was then purified by preparative HPLC eluting with water (0.05% TFA) and ACN (15-45% gradient, 0.035% TFA). The pure fractions were combined, evaporated to a minimal volume, and lyophilized to give a TFA salt of the title compound as a brown solid (4.2 mg, 8.8%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.67 (m, 1 H), 2.05 (td, J=12.88, 7.33 Hz, 1 H), 3.30-3.90 (m, 4 H), 3.78-3.99 (m, 2 H), 4.44 (s, 2 H), 6.49 (br s, 2 H), 7.54 (d, J=5.56 Hz, 1 H), 7.85 (br s, 2 H), 8.67-8.80 (m, 2 H). [M+H] calc'd for C16H16F4N6O2, 401; found, 401.

Workup

  1. customIn a 10 mL sealed
  2. customThe cap was sealed
  3. customthe mixture was reacted at 100° C. for 16 h
  4. filtrationThe reaction mixture was subsequently filtered through a Buchner funnel
  5. customto remove
  6. dissolutionun-dissolved K2CO3
  7. washThe solids were washed with ACN (2×5 mL)
  8. customthe filtrate was evaporated
  9. customto give a residue, which
  10. customto remove the protecting groups
  11. customNext, TFA was evaporated from the reaction mixture
  12. customwas then purified by preparative HPLC
  13. washeluting with water (0.05% TFA) and ACN (15-45% gradient, 0.035% TFA)
  14. customevaporated to a minimal volume

Sources & evidence

ORD record
ord-3523ee710fd74404808d18a3b7faa4ab
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

Loading…