HCID 71582673, compound → HCID 89599795, compound

HRID 1629784Notes

Reaction equation

HRID 1629784 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[C:13](=[O:43])[NH:14][C@@:15]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH2:37][CH2:38][C:39]([F:42])([F:41])[F:40])=[CH:31][CH:30]=3)([C:25]([F:28])([F:27])[F:26])[CH2:16][C:17]=2[C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)=[O:11])=[CH:5][CH:4]=1>CO.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]([CH:12]2[CH:17]([C:18]3[CH:19]=[CH:20][C:21]([CH3:24])=[CH:22][CH:23]=3)[CH2:16][C:15]([C:29]3[CH:30]=[CH:31][C:32]([O:35][CH2:36][CH2:37][CH2:38][C:39]([F:42])([F:41])[F:40])=[CH:33][CH:34]=3)([C:25]([F:26])([F:27])[F:28])[NH:14][C:13]2=[O:43])=[O:11])=[CH:7][CH:8]=1

Participants

4

Reactant 1

HCID 71582673HCID 71582673, compound

Product 1

HCID 89599795HCID 89599795, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

To a solution of Example 6-2 (90 mg, 0.15 mol) in MeOH (2 mL) was added 10% palladium on carbon (5 mg). The mixture was stirred under hydrogen (50 psi) overnight. Additional palladium on carbon (5 mg) was added and the reaction was stirred under hydrogen (50 psi) for an additional 1 h. The catalyst was removed by filtration through a pad of Celite® and the solution was concentrated in vacuo. The products were partly separated by preparative HPLC (CH3CN/H2O/TFA). Fractions containing the two products were combined and separated by chiral HPLC method D to provide Example 16-1 and Example 16-2. Data for Example 16-1: LCMS Anal. Calc'd for C31H30F6N2O4 608.57, found [M+H] 609.2. 1H NMR (400 MHz, CD3OD) δ 1.97-2.14 (m, 2H), 2.25 (s, 3H), 2.32-2.46 (m, 2H), 2.54-2.69 (m, 2H), 3.17 (td, J=11.82, 3.85 Hz, 1H), 3.60 (d, J=11.54 Hz, 1H), 3.71 (s, 3H), 4.10 (t, J=6.05 Hz, 2H), 6.76 (d, J=8.79 Hz, 2H), 6.99-7.12 (m, 6H), 7.13-7.23 (m, 2H), 7.55 (d, J=8.79 Hz, 2H). Analytical chiral HPLC method D RT=6.75 min, 99% ee. Data for Example 16-2: LCMS Anal. Calc'd for C31H30F6N2O4 608.57, found [M+H] 609.2. 1H NMR (400 MHz, CD3OD) δ 7.52 (d, J=8.8 Hz, 2H), 7.25-7.20 (m, 2H), 7.19-7.15 (m, 2H), 7.14-7.10 (m, 2H), 7.02-6.97 (m, 2H), 6.81-6.75 (m, 2H), 4.07 (t, J=6.0 Hz, 2H), 3.94-3.84 (m, 1H), 3.73 (s, 3H), 3.60 (d, J=12.1 Hz, 1H), 2.90 (dd, J=14.8, 3.3 Hz, 1H), 2.45-2.32 (m, 2H), 2.31 (dd, 1H, overlaps with peak at δ 2.27), 2.27 (s, 3H), 2.08-1.98 (m, 2H). Preparative chiral HPLC method D: RT=10.9 min, 99% ee.

Workup

  1. stirringthe reaction was stirred under hydrogen (50 psi) for an additional 1 h
  2. customThe catalyst was removed by filtration through a pad of Celite®
  3. concentrationthe solution was concentrated in vacuo
  4. customThe products were partly separated by preparative HPLC (CH3CN/H2O/TFA)
  5. additionFractions containing the two products
  6. customseparated by chiral HPLC method D
  7. customto provide Example 16-1 and Example 16-2

Sources & evidence

ORD record
ord-01feb733e3f8419eb17487e37ca8336e
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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