HCID 53956777, compound → HCID 10347790, compound

HRID 1386776Notes

Reaction equation

HRID 1386776 reaction equation
C([O:8][C:9](=[O:47])[C@H:10]([N:16]1[CH2:20][C@H:19]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=2)[C@@H:18]([CH2:28][N:29]2[CH2:34][CH2:33][CH:32]([CH2:35][CH2:36][C:37]([F:46])([F:45])[C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH2:31][CH2:30]2)[CH2:17]1)[CH2:11][CH:12]1[CH2:15][CH2:14][CH2:13]1)C1C=CC=CC=1>C(O)C.[OH-].[OH-].[Pd+2]>[F:46][C:37]([F:45])([C:38]1[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=1)[CH2:36][CH2:35][CH:32]1[CH2:33][CH2:34][N:29]([CH2:28][C@@H:18]2[C@@H:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)[CH2:20][N:16]([C@H:10]([CH2:11][CH:12]3[CH2:15][CH2:14][CH2:13]3)[C:9]([OH:47])=[O:8])[CH2:17]2)[CH2:30][CH2:31]1

Participants

4

Reactant 1

HCID 53956777HCID 53956777, compound

Product 1

HCID 10347790HCID 10347790, compound

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

2-(R)-(3-(S)-((4-(3,3-Difluoro-3-(4fluorophenyl)propyl) piperidin-1-yl)methyl)-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-3-(cyclobutyl)propanoic acid benzyl ester (170 mg, 0.261 mmol, from EXAMPLE 155, Step I) dissolved in 95% ethanol (15 mL) was hydrogenated at atmospheric pressure using 20% Pd(OH)2/C (35 mg). After 1 h, the mixture was filtered, the catalyst was washed with 95% ethanol, and the filtrate was evaporated. The crude product was purified by flash column chromatography on silica gel eluting with 95:5:1 v/v/v CH2Cl2/CH3OH/NH4OH followed by 90:10:1 v/v/v CH2Cl2/CH3OH/NH4OH to give the title compound as 137 mg of amorphous glass which could be recrystallized from CH3OH: 1H NMR (500 MHz, CD3OD) δ 7.49 (dd, J=9, 5, 2H), 7.39-7.33 (m, 1H), 7.19-7.11 (m, 4H), 7.01 (td, J=8, 2, 1H), 3.63 (dd, J=11, 8, 1H), 3.57 (bt, J=10, 1H), 3.42 (dd, J=9,4, 1H), 3.39-3.26 (m, 2H), 3.15 (bq, J=10, 1H), 2.89 (d, J=11, 1H), 2.77-2.66 (m, 2H), 2.54-2.44 (m, 2H), 2.35 (dd, J=13, 4, 1H), 2.22-2.06 (m, 4H), 2.03-1.54 (m, 10H), 1.31-1.00 (m, 5H); ESI-MS 561 (M+H); HPLC A: 2.72 min.

Workup

  1. filtrationthe mixture was filtered
  2. washthe catalyst was washed with 95% ethanol
  3. customthe filtrate was evaporated
  4. customThe crude product was purified by flash column chromatography on silica gel eluting with 95:5:1 v/v/v CH2Cl2/CH3OH/NH4OH

Sources & evidence

ORD record
ord-cde76cb2f14a491d98f2c7961eb93f21
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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