Diethyl cyanophosphonate → 1-tert-Butyl 2-methyl (2S,4S)-4-{[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino}pyrrolidine-1,2-dicarboxylate

HRID 602466Notes

Reaction equation

HRID 602466 reaction equation
[CH:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([OH:15])=O)=[N:5]1)([CH3:3])[CH3:2].[NH2:16][C@@H:17]1[CH2:21][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@H:19]([C:29]([O:31][CH3:32])=[O:30])[CH2:18]1.C(P(=O)(OCC)OCC)#N.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([NH:16][C@@H:17]2[CH2:21][N:20]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[C@H:19]([C:29]([O:31][CH3:32])=[O:30])[CH2:18]2)=[O:15])=[N:5]1)([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 76257Diethyl cyanophosphonateHCID 81531DiisopropylethylamineHCID 5200425(2S,4S)-1-Tert-butyl 2-methyl 4-aminopyrrolidine-1,2-dicarboxylateHCID 106796951-Isopropyl-1H-indazole-3-carboxylic acid

Product 1

HCID 866241491-tert-Butyl 2-methyl (2S,4S)-4-{[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino}pyrrolidine-1,2-dicarboxylateYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1-isopropyl-1H-indazole-3-carboxylic acid (300 mg, 1.47 mmol) and 1-tert-butyl 2-methyl (2S,4S)-4-aminopyrrolidine-1,2-dicarboxylate (396 mg, 1.62 mmol, Bioorg. Med. Chem., 2002, 10, 1399-1415) in N,N-dimethylformamide (15 mL) were added diethyl cyanophosphonate (0.27 mL, 1.76 mmol) and N,N-diisopropylethylamine (0.31 mL, 1.76 mmol) at room temperature. The resulting mixture was stirred for 14 h at the same temperature and concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate (200 mL), and the solution was washed with water (50 mL×2), brine (50 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (3:1) to give 618 mg (98%) of the title compound as a white amorphous solid.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe resulting residue was diluted with ethyl acetate (200 mL)
  3. washthe solution was washed with water (50 mL×2), brine (50 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (3:1)

Sources & evidence

ORD record
ord-0e325bb512014c9ca763594c0fc0de23
Source dataset
uspto-grants-2011_03
Patent number
US07906532B2

Reaction notes

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