HCID 68573765, compound → HCID 46880968, compound

HRID 2069188Notes

Reaction equation

HRID 2069188 reaction equation
C(OC([N:8]1[CH2:12][C@H:11]([O:13][CH2:14][CH2:15][N:16](C(OC(C)(C)C)=O)[CH2:17][CH2:18][O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)[C@H:10]([CH2:34][C:35]2[CH:40]=[C:39]([CH3:41])[CH:38]=[C:37]([N:42](CC3C=CC=CC=3)C(OC(C)(C)C)=O)[N:36]=2)[CH2:9]1)=O)(C)(C)C>CCO.[OH-].[OH-].[Pd+2]>[CH3:41][C:39]1[CH:38]=[C:37]([NH2:42])[N:36]=[C:35]([CH2:34][CH:10]2[CH:11]([O:13][CH2:14][CH2:15][NH:16][CH2:17][CH2:18][O:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[CH2:12][NH:8][CH2:9]2)[CH:40]=1

Participants

4

Reactant 1

HCID 68573765HCID 68573765, compound

Product 1

HCID 46880968HCID 46880968, compound

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent2×

Procedure

To a solution of 17a (30 mg, 39 μmol) in EtOH (5.0 mL) was added a 1:1 mixture of EtOH/concentrated HCl (10 mL) and Pd(OH)2/C (20%, 30 mg). The mixture was charged with H2 under the pressure of 500 psi. The reaction mixture was allowed to stir at room temperature for 40 h. The catalyst was removed by filtration through Celite, and the resulting Celite cake was washed with EtOH (4×3 mL) and 2 N HCl (3 mL). The combined filtrates were concentrated to yield inhibitor 2a, a yellow solid, as a hydrochloride salt (15 mg, 85%): 1H NMR (500 MHz, D2O) δ 2.08 (s, 3H), 2.60-2.63 (m, 2H), 2.70-2.80 (m, 1H), 2.97-3.03 (m, 1H), 3.13-3.16 (m, 1H), 3.17-3.37 (m, 3H), 3.38-3.50 (m, 3H), 3.54 (br s, 1H), 3.73 (br s, 1H), 4.05 (br s, 1H), 4.17 (br s, 2H), 6.33 (s, 1H), 6.44 (s, 1H), 6.50-6.55 (br s, 1H), 6.58-6.70 (m, 3H), 7.06-7.08 (m, 1H); 13C NMR (125 MHz, D2O) δ 21.3, 29.4, 41.7, 46.6, 47.0, 47.3, 49.5, 63.0, 64.0, 78.6, 108.4, 108.6, 108.7, 110.4, 110.5, 114.3, 130.9, 131.0, 145.8, 154.0, 158.3, 158.7, 158.8, 162.4, 164.4; LCQ-MS (M+H+) calcd for C21H30FN4O2 389. found 389; LC-TOF (M+H+) calcd for C21H30FN4O2 389.23473. found 389.23444.

Workup

  1. additionThe mixture was charged with H2 under the pressure of 500 psi
  2. customThe catalyst was removed by filtration through Celite
  3. washthe resulting Celite cake was washed with EtOH (4×3 mL) and 2 N HCl (3 mL)
  4. concentrationThe combined filtrates were concentrated

Sources & evidence

ORD record
ord-eb90e38557184dee9c48c8b82964e86c
Source dataset
uspto-grants-2012_10
Patent number
US08299100B2

Reaction notes

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