Acetic Acid → (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-morpholin-3-yl)propan-2-yl)-4-phenylbutanamide

HRID 132968Notes

Reaction equation

HRID 132968 reaction equation
C(N[C@]1([C@@H](CC)C)CCN([C@@H](CCC2C=CC=CC=2)C(N[C@@H](CC2C=C(F)C=C(F)C=2)[C@@H]([C@H]2C[C@@H](O)CN2C(C2C=CC=CC=2)C2C=CC=CC=2)O)=O)C1=O)(=[O:3])C.[C:58]([NH:61][C@:62]1([C@@H:111]([CH2:113][CH3:114])[CH3:112])[CH2:66][CH2:65][N:64]([C@@H:67]([CH2:102][CH2:103][C:104]2[CH:109]=[CH:108][CH:107]=[CH:106][CH:105]=2)[C:68]([NH:70][C@@H:71]([CH2:93][C:94]2[CH:99]=[C:98]([F:100])[CH:97]=[C:96]([F:101])[CH:95]=2)[C@@H:72]([C@H:74]2[CH2:79]CCC[N:75]2[CH:80]([C:87]2C=CC=CC=2)C2C=CC=CC=2)[OH:73])=[O:69])[C:63]1=[O:110])(=[O:60])[CH3:59].C(O)(=O)C.[H][H]>CO.[Pd]>[C:58]([NH:61][C@:62]1([C@@H:111]([CH2:113][CH3:114])[CH3:112])[CH2:66][CH2:65][N:64]([C@@H:67]([CH2:102][CH2:103][C:104]2[CH:105]=[CH:106][CH:107]=[CH:108][CH:109]=2)[C:68]([NH:70][C@@H:71]([CH2:93][C:94]2[CH:99]=[C:98]([F:100])[CH:97]=[C:96]([F:101])[CH:95]=2)[C@H:72]([OH:73])[C@H:74]2[CH2:79][O:3][CH2:87][CH2:80][NH:75]2)=[O:69])[C:63]1=[O:110])(=[O:60])[CH3:59]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 69194179(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamideHCID 69196374(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamideHCID 178418361HCID 178418361, compound

Product 1

HCID 69195838(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-morpholin-3-yl)propan-2-yl)-4-phenylbutanamideYield 58.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Step 16 (B): To 20 mg of 10% Pd/C was added a solution of the entire sample of the compound of step 16 (A) in 5 ml of MeOH under nitrogen. A 0.3 ml portion of acetic acid was added. The mixture was shaken in a Parr apparatus with 50 psi of hydrogen for 3.5 hours. The suspension was filtered over Celite, and the product was purified by HPLC under standard conditions to give 30 mg (58.8% yield for the two steps) of the title compound of Example 16. 1H NMR (500 MHz, CDCl3) δ ppm 0.90 (d, J=6.71 Hz, 3 H) 1.02 (t, J=7.17 Hz, 3 H) 1.13 (m, 1 H) 1.72 (m, 2 H) 2.00 (s, 3 H) 2.12 (m, 1 H) 2.21 (q, J=7.12 Hz, 2 H) 2.38 (m, 1 H) 2.57 (m, 1 H) 2.74 (m, 2 H) 3.23 (dd, J=14.34, 2.75 Hz, 1 H) 3.31 (m, 5 H) 3.42 (m, 2 H) 3.70 (m, 1 H) 3.77 (m, 1 H) 3.91 (m, 2 H) 3.99 (m, 2 H) 4.21 (dd, J=12.51, 3.05 Hz, 1 H) 6.73 (tt, J=9.16, 2.14 Hz, 1 H) 6.87 (d, J=7.94 Hz, 2 H) 7.19 (d, J=5.80 Hz, 3 H) 7.27 (m, 2 H) 8.12 (s, 1 H) 8.25 (d, J=8.85 Hz, 1 H).

Workup

  1. filtrationThe suspension was filtered over Celite
  2. customthe product was purified by HPLC under standard conditions

Sources & evidence

ORD record
ord-ac6140e3daea42d1944b794385fc5d9d
Source dataset
uspto-grants-2008_06
Patent number
US07388007B2

Reaction notes

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