Hydrochloric Acid → HCID 74983213, compound

HRID 1915921Notes

Reaction equation

HRID 1915921 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

Procedure

To a 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 2) (28 mg, 0.042 mmol) in MeOH (2 mL) was added a solution of HCl in dioxane (4 M, 1.1 mL, 4.24 mmol) and the mixture was stirred at room temperature for 18 hr. The solvent was removed under reduced pressure and the residue was dissolved in MeOH/water (3 mL/3 mL), treated with K2CO3 (29 mg, 0.21 mmol) and heated at 60° C. for 18 hr. The MeOH was removed under reduced pressure and the aqueous residue was extracted with 5% MeOH/DCM (2×40 mL). The organic layers were combined, passed through a phase separation cartridge and concentrated under reduced pressure to give 358 (Diastereomer 2) as an off-white solid (17 mg, 86% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.76 (s, 1H), 7.34-7.29 (m, 1H), 7.03 (t, J=8.7 Hz, 2H), 6.11 (s, 2H), 4.47-4.29 (m, 1H), 3.83 (s, 3H), 3.23-3.12 (m, 1H), 2.86-2.75 (m, 1H), 2.25-1.84 (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 (3 mL/3 mL)
  3. temperatureheated at 60° C. for 18 hr
  4. customThe MeOH was removed under reduced pressure
  5. extractionthe aqueous residue was extracted with 5% MeOH/DCM (2×40 mL)
  6. custompassed through a phase separation cartridge
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0bbfb6f9f32c414cac8c7c84c440b989
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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