Hydrochloric Acid → HCID 74983213, compound

HRID 1915920Notes

Reaction equation

HRID 1915920 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][C:11]([NH:38]C(=O)OC(C)(C)C)=[C:12]([C:14](=[O:37])[NH:15][C:16]2[CH:17]=[N:18][N:19]([CH3:36])[C:20]=2[CH:21]2[CH2:27][CH2:26][CH:25]([NH:28]C(=O)C(F)(F)F)[CH:24]([F:35])[CH2:23][CH2:22]2)[N:13]=1.Cl.O1CCOCC1.C([O-])([O-])=O.[K+].[K+]>CO>[NH2:38][C:11]1[S:10][C:9]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])=[N:13][C:12]=1[C:14]([NH:15][C:16]1[CH:17]=[N:18][N:19]([CH3:36])[C:20]=1[CH:21]1[CH2:22][CH2:23][C@@H:24]([F:35])[C@H:25]([NH2:28])[CH2:26][CH2:27]1)=[O:37]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 86680121HCID 86680121, compound

Product 1

HCID 74983213HCID 74983213, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution/suspension of tert-butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)cycloheptyl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (Diastereomer 1) (49 mg, 0.074 mmol) in MeOH (2 mL) was added a solution of HCl in dioxane (4 M, 1.9 mL, 7.42 mmol) and the mixture was heated at 60° C. for 72 hr. The solvent was removed under reduced pressure and the residue was dissolved in MeOH/water (5 mL/5 mL) and treated with K2CO3 (51 mg, 0.37 mmol). The mixture was heated at 65° C. for 18 hr. The MeOH was removed under reduced pressure and the aqueous residue was extracted with 5% MeOH/DCM (2×30 mL). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure. The residue was dissolved in MeOH and loaded onto an SCX column. The column was washed with MeOH, eluted with 3 N ammonia in MeOH and the solvent removed under reduced pressure to give 357 (Diastereomer 1) as a beige solid (10 mg, 29% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.76 (s, 1H), 7.35-7.28 (m, 1H), 7.07-6.99 (m, 2H), 6.11 (s, 2H), 4.46-4.29 (m, 1H), 3.83 (s, 3H), 3.23-3.13 (m, 1H), 2.84-2.76 (m, 1H), 2.26-1.81 (m, 6H), 1.60-1.40 (m, 2H). Alkyl NH2 not observed. LCMS (ES+) m/z 465 (M+1)

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in MeOH/water (5 mL/5 mL)
  3. temperatureThe mixture was heated at 65° C. for 18 hr
  4. customThe MeOH was removed under reduced pressure
  5. extractionthe aqueous residue was extracted with 5% MeOH/DCM (2×30 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in MeOH
  9. washThe column was washed with MeOH
  10. washeluted with 3 N ammonia in MeOH
  11. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-4db0557faccc4e438740a5727a11bf0a
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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