Diisopropylethylamine → (S)-tert-butyl 1-((S)-1-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl)pyrrolidine-2-carbonyl)pyrrolidine-2-carboxylate

HRID 594190Notes

Reaction equation

HRID 594190 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:7].[C:20]1(=[O:34])[N:24]([CH:25]([CH2:29][CH2:30][CH2:31][CH3:32])C(O)=O)[C:23](=[O:33])[CH:22]=[CH:21]1.CCN(C(C)C)C(C)C.CN([C:47]([O:51]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(OCC)(=O)C>[O:34]=[C:20]1[CH:21]=[CH:22][C:23](=[O:33])[N:24]1[CH2:25][CH2:29][CH2:30][CH2:31][CH2:32][C:47]([N:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:7])=[O:51]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15598548(S)-tert-butyl 1-((S)-pyrrolidine-2-carbonyl)pyrrolidine-2-carboxylateHCID 22352954Maleimidocaproic acid

Product 1

HCID 67453011(S)-tert-butyl 1-((S)-1-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl)pyrrolidine-2-carbonyl)pyrrolidine-2-carboxylateYield 33%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of the amine 74 (200 mg, 0.75 mmol), 39 (190 mg, 0.9 mmol) and DIPEA (0.32 mL, 1.8 mmol) was added HATU (342 mg, 0.9 mmol) and the mixture was allowed to stir at an ambient temperature for 5 h. The mixture was poured into ethyl acetate (100 mL) and washed with water (3×100 mL) and brine (1×100 mL). The organic phase was dried over magnesium sulfate, filtered and concentrated. The resulting residue was subjected to radial chromatography on a 2 mm radial chromatotron plate eluting with dichloromethane followed by an increasing gradient of 1 to 5% methanol in dichloromethane. Two additional purifications, both eluting with a gradient of 1 to 5% methanol in dichloromethane, first on a 2 mm plate and then on a 1 mm plate afforded 113 mg (33%) of 77 as an white solid: 1H-NMR (400 MHz, CDCl3) δ 4.63 (m, 1H), 4.41 (m, 1H), 3.82 (m, 1H), 3.63 (m, 1H), 3.55 (m, 1H), 3.45 (m, 3H), 2.38-1.83 (m, 10H), 1.70-1.50 (m, 5H), 1.45 (m, 9H), 1.35 (m, 2H); MS (ES+) m/z 462.33 [M+H]+.

Workup

  1. washwashed with water (3×100 mL) and brine (1×100 mL)
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. washeluting with dichloromethane

Sources & evidence

ORD record
ord-503beda4bbc84dcf9e5ec009cfc17164
Source dataset
uspto-grants-2016_01
Patent number
US09242013B2

Reaction notes

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