HCID 86758720, compound → HCID 18342548, compound

HRID 2301178Notes

Reaction equation

HRID 2301178 reaction equation
[CH2:1]([N:4]([CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][C@@H:18]2[C@@H:22]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[CH2:21][N:20]([C@@H:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]3[CH2:36][C:37]([O:39]CC3C=CC=CC=3)=[O:38])[CH2:19]2)[CH2:13][CH2:12]1)[C:5]1[N:10]=[CH:9][CH:8]=[CH:7][N:6]=1)[CH2:2][CH3:3].[H][H]>CO.[Pd]>[CH2:1]([N:4]([CH:11]1[CH2:12][CH2:13][N:14]([CH2:17][C@@H:18]2[C@@H:22]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[CH2:21][N:20]([C@@H:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH:31]3[CH2:36][C:37]([OH:39])=[O:38])[CH2:19]2)[CH2:15][CH2:16]1)[C:5]1[N:6]=[CH:7][CH:8]=[CH:9][N:10]=1)[CH2:2][CH3:3]

Participants

5

Reactant 2

HCID 86758720HCID 86758720, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 18342548HCID 18342548, compoundYield 85.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of 2-(R)-(3-(S)-((4-(N-(prop-1-yl)-N-(pyrimid-2-yl)amino)-piperidin-1-yl)methyl)-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)cyclohexylacetic acid, benzyl ester (80 mg, 0.13 mmol) from Example 25 Step A, in 3.0 mL of MeOH was hydrogenated using 10% palladium on carbon (20 mg, 0.026 mmol) under one atmosphere of hydrogen gas. After TLC indicated the absence of the starting benzyl ester, the reaction was filtered through a 0.45 micron nylon membrane polypropylene filter and concentrated under reduced pressure to give 60 mg (80%) of the title compound as a white solid. HPLC (Zorbax SB-C8 column, 4.6 mm×7.5 cm, Gradient: 90 H2O:10 CH3CN to 0 H2O:100 CH3CN over 7.5 minutes then hold at 100 CH3CN:0 H2O for 45 seconds, 2.25 mL/min, 220 nm): Retention Time: 3.4 minutes. ESI-MS: 538.0 (M+1). 1H NMR (500 MHz, CDCl3): δ 0.89-0.92 (t, J=7.4 Hz, 3H), 1.20-3.42 (25H), 3.87 (1H), 4.59 (1H), 6.42-6.43 (t, J=4.8 Hz, 1H), 6.91-6.95 (t, J=6.4 Hz, 1H), 7.03-7.09 (m, 2H), 7.24-7.31 (m, 1H), 8.24-8.25 (d, J=4.6 Hz, 2H).

Workup

  1. filtrationthe reaction was filtered through a 0.45 micron nylon membrane polypropylene
  2. filtrationfilter
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d851977cd7ba4940b2ff0821315feef5
Source dataset
uspto-grants-2002_12
Patent number
US06498161B1

Reaction notes

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