Triethylamine → HCID 11951919, compound

HRID 507855Notes

Reaction equation

HRID 507855 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH:11]2[CH2:12][CH2:13][CH:7]1[CH2:8][CH:9]([N:14]1[CH2:19][CH2:18][CH:17]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH2:16][CH2:15]1)[CH2:10]2)=[O:5])[CH3:2].CCN(CC)CC.[CH:35]1([C:41](Cl)=[O:42])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1.[OH-].[Na+]>C(Cl)Cl>[CH2:1]([O:3][C:4]([N:6]1[CH:11]2[CH2:12][CH2:13][CH:7]1[CH2:8][CH:9]([N:14]1[CH2:15][CH2:16][CH:17]([N:20]([C:41]([CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)=[O:42])[C:21]3[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=3)[CH2:18][CH2:19]1)[CH2:10]2)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 75938Cyclohexanecarbonyl chlorideHCID 11951743HCID 11951743, compound

Product 1

HCID 11951919HCID 11951919, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-[4-(4-Fluoro-phenylamino)-piperidin-1-yl]-8-azabicyclo[3.2.1]octane-8-carboxylic acid ethyl ester (50 mg; 0.13 mmol; 1 eq.) was dissolved in DCM (3 mL) and Et3N (0.056 mL; 0.39 mmol; 3 eq.) was added. Cyclohexylcarbonyl chloride (30 mg; 0.2 mmol; 2 eq.) was then added and the solution was stirred at room temperature for 18 hours (overnight). 1N NaOH (10 mL) was added and the solution was extracted with EtOAc (2×20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified using reversed-phase HPLC (2-99% CH3CN/H2O gradient with 0.05% TFA). LC/MS M/Z=432.4, Retention time=2.12; 10-99% CH3CN/H2O gradient with 0.05% TFA over 5 minutes. H NMR (400 MHz, MeOD, TFA salt) δ 7.33-7.22 (m, 4H), 4.75 (tt, J=12.3 Hz, 3.8 Hz, 1H), 4.39 (s, 2H), 4.14 (q, J=7.1 Hz, 2H), 3.75-3.58 (m, 3H), 3.09 (t, J=11.9 Hz, 2H), 2.14-1.89 (m, 7H), 1.79-1.40 (m, 14H), 1.27 (t, J=7.1 Hz, 3H), 1.26-1.11 (m, 1H), 1.02-0.90 (m, 2H).

Workup

  1. extractionthe solution was extracted with EtOAc (2×20 mL)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified
  6. wait10-99% CH3CN/H2O gradient with 0.05% TFA over 5 minutes

Sources & evidence

ORD record
ord-9216e1056ab04ae1b2e787f043637f51
Source dataset
uspto-grants-2010_08
Patent number
US07786308B2

Reaction notes

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