Pyrrolidine → HCID 67492317, compound

HRID 1945530Notes

Reaction equation

HRID 1945530 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:6]([O:10][C:11]([N:13]1[CH2:17][CH2:16][C@H:15]([C:18]([OH:20])=O)[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].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>CN(C=O)C>[C:6]([O:10][C:11]([N:13]1[CH2:17][CH2:16][C@H:15]([C:18]([N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:20])[CH2:14]1)=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 1512492(3S)-1-[(tert-butoxy)carbonyl]pyrrolidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 67492317HCID 67492317, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Pyrrolidine (51 μL, 1.03 mmol) was added to a solution of (S)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (200 mg, 0.93 mmol), HATU (391 mg, 1.03 mmol) and DIPEA (410 μL, 2.35 mmol) in DMF and the resulting mixture stirred at ambient temperature for 1 h, then concentrated in vacuo. The resulting oil was partitioned between EtOAc and water. The organic layer was separated, washed with water and brine, then dried (MgSO4) and concentrated in vacuo to give (S)-3-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylic acid tert-butyl ester as a colourless oil. TFA (3 mL) was added to a solution of (S)-3-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylic acid tert-butyl ester in DCM (10 mL) and the mixture stirred at ambient temperature for 1 h, then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo to afford the title compound as a pale brown oil (110 mg, 70%). 1H NMR (CDCl3, 400 MHz) δ 4.01 (m, 3 H); 3.52-3.41 (m, 3 H); 3.25-3.11 (m, 2 H); 3.10-2.97 (m, 2 H); 2.89 (dt, J=11.4, 7.5 Hz, 1 H); 2.11-1.99 (m, 1 H); 2.01-1.91 (m, 2 H) and 1.93-1.82 (m, 2 H).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe resulting oil was partitioned between EtOAc and water
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6404ae9eba46458289936aea8dce4bbc
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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