Sodium Thiosulfate → methyl (3R,4S)-3-[(3,6-diethyl-5-iodopyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate

HRID 1063272Notes

Reaction equation

HRID 1063272 reaction equation
[CH2:1]([C:3]1[C:4]([NH:11][C@H:12]2[C@@H:16]([O:17][CH2:18][CH3:19])[CH2:15][N:14]([C:20]([O:22][CH3:23])=[O:21])[CH2:13]2)=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2].[I:24]N1C(=O)CCC1=O.S([O-])([O-])(=O)=S.[Na+].[Na+]>CN(C=O)C>[CH2:1]([C:3]1[C:4]([NH:11][C@H:12]2[C@@H:16]([O:17][CH2:18][CH3:19])[CH2:15][N:14]([C:20]([O:22][CH3:23])=[O:21])[CH2:13]2)=[N:5][C:6]([CH2:9][CH3:10])=[C:7]([I:24])[N:8]=1)[CH3:2]

Participants

5

Reactant 3

HCID 24477Sodium ThiosulfateHCID 120273N-IodosuccinimideHCID 86591414methyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate

Product 1

HCID 86591415methyl (3R,4S)-3-[(3,6-diethyl-5-iodopyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of the methyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate (5.25 g, 16.2 mmole) in DMF (0.3M, 54 ml) under N2 was added N-iodosuccinimide (4.57, 1.25 eq.). The reaction mixture was heated at 50° C. for 2 hours then cooled to ambient temperature. It was poured into saturated sodium thiosulfate (100 mL) and extracted with ethyl acetate (2×100 ml), dried with MgSO4, filtered and concentrated. Purification with Biotage MPLC (40 g, 10-30% ethyl acetate in heptane gradient) provided 6.45 g (89%) of methyl (3R,4S)-3-[(3,6-diethyl-5-iodopyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate as a white solid. 1H NMR (400 MHz, CDCl3) δ 5.06 (m, 1 H), 4.62 (m, 1 H), 4.05 (m, 1 H), 3.88 (m, 1 H), 3.73 (m, 5 H), 3.58 (m, 1 H), 3.43 (m, 1 H), 3.18 (m, 1 H), 2.80 (m, 2 H), 2.62 (q, J=15.8 Hz, 2 H), 1.26 (m, 9 H); IR (diffuse reflectance) 3432, 2976, 2969, 2498, 2461, 2388, 2350, 2337, 1697, 1550, 1535, 1457, 1451, 1392, 771 (s) cm−1 HRMS (ESI) calcd for C16H25N4O3I+H1 449.1051. found 449.1029. Anal. Calcd for C16 H25 I N4 O3: C, 42.87; H, 5.62; N, 12.50. Found: C, 43.01; H, 5.73; N, 12.43.

Workup

  1. temperaturethen cooled to ambient temperature
  2. extractionextracted with ethyl acetate (2×100 ml)
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification with Biotage MPLC (40 g, 10-30% ethyl acetate in heptane gradient)

Sources & evidence

ORD record
ord-0384ca4b53754861886eaf80ca52c3e9
Source dataset
uspto-grants-2005_11
Patent number
US06964965B2

Reaction notes

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