Diisopropylethylamine → Methyl (S)-1-((S)-2-(4-(((4-((S)-1-((R)-2-(diethylamino)-2-phenylacetyl)pyrrolidine-2-carboxamido)benzyl)(phenyl)amino)methyl)phenylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamate

HRID 923383Notes

Reaction equation

HRID 923383 reaction equation
[CH3:1][C:2]([CH3:49])([CH3:48])[C@H:3]([NH:43][C:44](=[O:47])[O:45][CH3:46])[C:4](=[O:42])[N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10](=[O:41])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][N:19]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([NH:27][C:28]([C@@H:30]3[CH2:34][CH2:33][CH2:32][NH:31]3)=[O:29])=[CH:23][CH:22]=2)=[CH:14][CH:13]=1.[CH2:50]([N:52]([CH2:63][CH3:64])[C@H:53]([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:54](O)=[O:55])[CH3:51].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CS(C)=O.O>[CH2:63]([N:52]([CH2:50][CH3:51])[C@H:53]([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:54]([N:31]1[CH2:32][CH2:33][CH2:34][C@H:30]1[C:28]([NH:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][N:19]([CH2:18][C:15]2[CH:14]=[CH:13][C:12]([NH:11][C:10]([C@@H:6]3[CH2:7][CH2:8][CH2:9][N:5]3[C:4](=[O:42])[C@@H:3]([NH:43][C:44](=[O:47])[O:45][CH3:46])[C:2]([CH3:49])([CH3:48])[CH3:1])=[O:41])=[CH:17][CH:16]=2)[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)=[CH:22][CH:23]=1)=[O:29])=[O:55])[CH3:64]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1091378(R)-2-(diethylamino)-2-phenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59540386Methyl (S)-3,3-dimethyl-1-oxo-1-((S)-2-(4-((phenyl(4-((S)-pyrrolidine-2-carboxamido)benzyl)amino)methyl)phenylcarbamoyl)pyrrolidin-1-yl)butan-2-ylcarbamate

Product 1

HCID 59540276Methyl (S)-1-((S)-2-(4-(((4-((S)-1-((R)-2-(diethylamino)-2-phenylacetyl)pyrrolidine-2-carboxamido)benzyl)(phenyl)amino)methyl)phenylcarbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamateYield 58.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

The product from Example 10A (15 mg, 0.022 mmol) was combined with (R)-2-(diethylamino)-2-phenylacetic acid (6.04 mg, 0.029 mmol), HATU (9.38 mg, 0.025 mmol) and Hunig's base (0.024 mL, 0.135 mmol) in DMSO (1.0 mL) and the mixture was stirred at room temperature for 45 min. Diluted with water and collected the solid by filtration. The product was purified by chromatography on silica gel, eluting with 0-5% MeOH in CH2Cl2 to give the title compound (11 mg, 57.2% yield). 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 0.87 (t, J=7.10 Hz, 6 H) 0.94 (s, 9 H) 1.59-1.68 (m, 1 H) 1.78-1.86 (m, 2 H) 1.92-2.00 (m, 1 H) 2.04-2.12 (m, 2 H) 2.43-2.52 (m, 2 H) 2.55-2.67 (m, 4 H) 3.23-3.30 (m, 1 H) 3.56-3.61 (m, 2 H) 3.62 (s, 3 H) 3.71-3.78 (m, 1 H) 4.30 (d, J=9.61 Hz, 1 H) 4.48 (s, 4 H) 4.55 (s, 1 H) 4.72-4.77 (m, 2 H) 5.31 (d, J=9.77 Hz, 1 H) 6.63 (t, J=7.25 Hz, 1 H) 6.67 (d, J=7.93 Hz, 2 H) 7.06-7.12 (m, 6 H) 7.24-7.32 (m, 3 H) 7.33 (d, J=8.54 Hz, 2 H) 7.35-7.42 (m, 4 H) 9.22 (s, 1 H) 9.64 (s, 1 H).

Workup

  1. customcollected the solid
  2. filtrationby filtration
  3. customThe product was purified by chromatography on silica gel
  4. washeluting with 0-5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-af6de4df8654409285e83eb0378fb260
Source dataset
uspto-grants-2016_03
Patent number
US09278922B2

Reaction notes

Loading…