Trifluoroacetic acid → HCID 53251177, compound

HRID 2092894Notes

Reaction equation

HRID 2092894 reaction equation
Cl[C:2]1[C:7]2[C:8](=[O:22])[N:9](CC3C=CC(OC)=CC=3OC)[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]2[NH:31]C(=O)OC(C)(C)C)[N:3]=1.[CH3:39][C:40]1[N:41]=[CH:42][NH:43][CH:44]=1.C([O-])([O-])=O.[K+].[K+].[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52]>C(#N)C>[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52].[NH2:31][C@H:26]1[CH2:27][CH2:28][CH2:29][CH2:30][C@H:25]1[NH:24][C:4]1[N:3]=[C:2]([N:43]2[CH:44]=[C:40]([CH3:39])[N:41]=[CH:42]2)[C:7]2[C:8](=[O:22])[NH:9][CH2:10][C:6]=2[C:5]=1[F:23]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 86654712tert-Butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamateHCID 178418800HCID 178418800, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 53251177HCID 53251177, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

In a 10 mL sealed cap glass vial, tert-butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (50 mg, 0.091 mmol), 4-methyl-1H-imidazole (22.43 mg, 0.273 mmol) and K2CO3 (50.3 mg, 0.364 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 solids. The solids were washed with ACN (2×5 mL) and the filtrate was evaporated to give a residue, which was treated with TFA (4 mL) and heated at 80° C. for 1 h to remove the protecting groups. Next, TFA was evaporated from the reaction mixture. The resulting residue was reconstituted in DMSO (5 mL) and purified via preparative HPLC eluting with water (0.05% TFA) and ACN (15-65% 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 white solid (7.2 mg, 23%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20-1.65 (m., 8H), 3.65-3.79 (m, 5H), 4.15 (s, 2H), 6.40 (d, 1H), 6.51 (d, 1H), 6.73 (m, 1H), 6.97 (d, 1H), 7.26 (d, 1H), 8.68 (br s, 1H). [M+H] calc'd for C17H21FN6O, 345. found, 345.

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 solids
  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. custompurified via preparative HPLC
  13. washeluting with water (0.05% TFA) and ACN (15-65% gradient, 0.035% TFA)
  14. customevaporated to a minimal volume

Sources & evidence

ORD record
ord-9a216eccfd864edd90133b50452d2529
Source dataset
uspto-grants-2013_05
Patent number
US08440689B2

Reaction notes

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