Acetic Acid → HCID 67270822, compound

HRID 601723Notes

Reaction equation

HRID 601723 reaction equation
[C:1]([NH:4][C@:5]1([C@@H:62]([CH2:64][CH3:65])[CH3:63])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:11]([NH:13][C@@H:14]([CH2:44][C:45]2[CH:50]=[C:49]([F:51])[CH:48]=[C:47]([F:52])[CH:46]=2)[C@@H:15]([C@H:17]2[CH2:26][C:25]3[C:20](=[C:21]([O:27][CH2:28][CH:29]=[CH2:30])[CH:22]=[CH:23][CH:24]=3)[CH2:19][N:18]2[CH:31]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[OH:16])=[O:12])[C:6]1=[O:61])(=[O:3])[CH3:2].C(O)(=O)C>CO.[Pd]>[C:1]([NH:4][C@:5]1([C@@H:62]([CH2:64][CH3:65])[CH3:63])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:11]([NH:13][C@@H:14]([CH2:44][C:45]2[CH:50]=[C:49]([F:51])[CH:48]=[C:47]([F:52])[CH:46]=2)[C@H:15]([OH:16])[C@H:17]2[CH2:26][C:25]3[C:20](=[C:21]([O:27][CH2:28][CH2:29][CH3:30])[CH:22]=[CH:23][CH:24]=3)[CH2:19][NH:18]2)=[O:12])[C:6]1=[O:61])(=[O:3])[CH3:2].[CH2:28]([O:27][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[C:20]=1[CH2:19][N:18]([CH:31]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[C@@H:17]([C@@H:15]([OH:16])[C@@H:14]([NH2:13])[CH2:44][C:45]1[CH:50]=[C:49]([F:51])[CH:48]=[C:47]([F:52])[CH:46]=1)[CH2:26]2)[CH:29]=[CH2:30]

Participants

6

Reactant 2

HCID 176Acetic AcidHCID 67271973HCID 67271973, compound

Product 2

HCID 59746638HCID 59746638, compoundYield 74%HCID 67270822HCID 67270822, compoundYield 147.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((R)-8-(allyloxy)-2-benzhydryl-1,2,3,4-tetrahydroisoquinolin-3-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamide (Step 3 (A), 50 mg) in MeOH (5 mL) was added a catalytic amount of Pd on activated charcoal (10 wt %) and acetic acid (0.2 mL). The reaction mixture was put on hydrogenator at 50 psi for 3.5 h. The mixture was then filtered and concentrated in vacuo and purified by silica gel Flash chromatography to give 30 mg of the title compound of compound 3 (74% yield). 1H NMR (CD3OD, 500 MHz) δ 0.76 (3H, d, J=5 Hz), 0.97-1.00 (3H, m), 1.04-1.07 (4H, m), 1.64-1.69 (2H, m), 1.78-1.85 (2H, m), 1.94 (1H, s), 1.97-2.03 (4H, m), 2.06-2.20 (3H, m), 2.38-2.44 (1H, m), 2.53-2.59 (1H, m), 2.78 (1H, dd, J=10, 15 Hz), 2.96 (1H, m), 3.10-3.20 (2H, m), 3.26-3.31 (2H, m), 3.42 (1H, dt, J=5, 10 Hz), 3.97 (2H, t, J=5 Hz), 4.01-4.05 (2H, m), 4.12 (1H, m), 4.22 (1H, dt, J=5, 10 Hz), 4.32 (1H, d, J=15 Hz), 6.75 (1H, m), 6.80 (2H, d, J=10 Hz), 6.92 (2H, d, J=5 Hz), 6.95 (2H, d, J=10 Hz), 7.10-7.19 (4H, m). MS (ESI) (M+H)+ 719.37.

Workup

  1. filtrationThe mixture was then filtered
  2. concentrationconcentrated in vacuo
  3. custompurified by silica gel Flash chromatography

Sources & evidence

ORD record
ord-412aa7fb5f9d473382ba26d69c511021
Source dataset
uspto-grants-2011_03
Patent number
US07902218B2

Reaction notes

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