Diisopropylethylamine → HCID 67329578, compound

HRID 1674555Notes

Reaction equation

HRID 1674555 reaction equation
[C:1]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][C@H:9]1[C:19](O)=[O:20])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(C(C)C)CC)(C)C.Cl.[NH2:32][C@:33]1([C:38]([NH:40][S:41]([CH:44]2[CH2:46][CH2:45]2)(=[O:43])=[O:42])=[O:39])[CH2:35][C@H:34]1[CH:36]=[CH2:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[CH:44]1([S:41]([NH:40][C:38]([C@@:33]2([NH:32][C:19]([C@@H:9]3[CH2:10][C@@H:11]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[CH2:12][N:8]3[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])=[O:20])[CH2:35][C@H:34]2[CH:36]=[CH2:37])=[O:39])(=[O:43])=[O:42])[CH2:46][CH2:45]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27559781-(1,1-Dimethylethyl) (2S,4S)-4-phenyl-1,2-pyrrolidinedicarboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 23595124(1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide hydrochloride

Product 1

HCID 67329578HCID 67329578, compoundYield 79.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (2S,4S)-Boc-4-phenylpyrrolidine-2-carboxylic acid (0.711 g 2.44 mmol) (purchased from Chem-Impex International, Inc.), diisopropylethylamine (0.948 g, 7.33 mmol), and cyclopropanesulfonic acid (1-(R)-amino-2-(S)-vinyl-cyclopropanecarbonyl)amide HCl salt (0.561 g, 2.44 mmol) in dichloromethane (24 mL) was added HATU (1.21 g, 3.18 mmol). After stirring the reaction mixture for 14 hours, it was washed with 5% aqueous NaHCO3 (50 mL), and 5% aqueous citric acid (50 mL). Each aqueous layer was sequentially extracted with 2×25 mL dichloromethane. The combined organic layer was dried over MgSO4, filtered, and concentrated. The resulting brown viscous oil was purified by flash column chromatography (SiO2, 97:3, dichloromethane:methanol) to give (2S,4S)-tert-butyl 2-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-4-phenylpyrrolidine-1-carboxylate as a brown foamy solid (0.973 g, 79% yield). 1H NMR (CD3OD, 500 MHz) δ 0.91 (br s, 1H), 1.03 (d, J=6.4 Hz, 1H), 1.16-1.23 (m, 1H), 1.31-1.38 (m, 1H), 1.44 (dd, J=9.6, 5.6 Hz, 1H), 1.48 (s, 4H), 1.52 (s, 5H), 1.89 (t, J=6.4 Hz), 2.09 (q, J=8.4 Hz, 0.4H), 2.19 (q, J=8.6 Hz, 0.6H), 2.85-2.90 (m, 0.4H), 2.92-2.97 (m, 0.6H), 3.44 (t, J=9.6 Hz, 1H), 3.65 (p, J=8.0 Hz, 1H), 3.93-4.01 (m, 1H), 4.29 (dd, J=10.1, 6.7 Hz, 1H), 5.12 (d, J=10.1 Hz, 1H), 5.30 (d, J=18.0 Hz, 1H), 5.75-5.82 (m, 1H), 7.24 (t, J=6.9 Hz, 1H), 7.29-7.33 (m, 5H); MS m/z 504 (M+Na).

Workup

  1. washit was washed with 5% aqueous NaHCO3 (50 mL), and 5% aqueous citric acid (50 mL)
  2. extractionEach aqueous layer was sequentially extracted with 2×25 mL dichloromethane
  3. dry with materialThe combined organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting brown viscous oil was purified by flash column chromatography (SiO2, 97:3, dichloromethane:methanol)

Sources & evidence

ORD record
ord-138a8c909c3a4a858b35e173996284cf
Source dataset
uspto-grants-2011_08
Patent number
US08003604B2

Reaction notes

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