Triethylamine → Ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-methylsulfonyloxy-butanoate

HRID 600549Notes

Reaction equation

HRID 600549 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].C(N(CC)CC)C.[N:13]1([C:17]([C:19]2[N:24]=[CH:23][C:22]([O:25][C:26]3[CH:27]=[C:28]([CH:39]=[C:40]([C:42](=[O:51])[NH:43][C:44]4[CH:49]=[N:48][C:47]([CH3:50])=[CH:46][N:45]=4)[CH:41]=3)[O:29][CH:30]([CH2:36][CH2:37][OH:38])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:21][CH:20]=2)=[O:18])[CH2:16][CH2:15][CH2:14]1>C(Cl)Cl>[N:13]1([C:17]([C:19]2[N:24]=[CH:23][C:22]([O:25][C:26]3[CH:27]=[C:28]([CH:39]=[C:40]([C:42](=[O:51])[NH:43][C:44]4[CH:49]=[N:48][C:47]([CH3:50])=[CH:46][N:45]=4)[CH:41]=3)[O:29][CH:30]([CH2:36][CH2:37][O:38][S:2]([CH3:1])(=[O:4])=[O:3])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:21][CH:20]=2)=[O:18])[CH2:14][CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59761144Ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-hydroxy-butanoate2×

Product 1

HCID 86621533Ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-methylsulfonyloxy-butanoateYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (13 L, 0.16 mmol) and triethylamine (34 μL, 0.24 mmol) were added to a solution of ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-hydroxy-butanoate (Intermediate 28) (65 mg, 0.12 mmol) in DCM (5 mL) at 0° C. under nitrogen. The reaction was allowed to warm to RT and stirred for 2 hours. The solvent was evaporated under reduced pressure and the residue partitioned between ethyl acetate (10 mL) and brine (10 mL). The organic layer was separated and the aqueous layer re-extracted with ethyl acetate (10 mL). The combined organics were dried (MgSO4), concentrated under reduced pressure and the residue purified by column chromatography on silica eluting with 0-10% methanol/DCM to give product (29 mg, 42%). 1H NMR δ (300 MHz, CDCl3) 1.23-1.30 (3H, m), 2.33-2.46 (4H, m), 2.56 (3H, s), 3.03 (3H, s), 4.22-4.29 (4H, m), 4.44-4.49 (2H, m), 4.71 (2H t), 4.87-4.91 (1H, m), 6.81 (1H t), 7.21 (1H t), 7.29 (1H t), 7.38-7.41 (1H, m), 8.13 (2H d), 8.34 (1H d), 8.42 (1H, s), 9.51 (1H, s); m/z 615 (M+H)+.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue partitioned between ethyl acetate (10 mL) and brine (10 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer re-extracted with ethyl acetate (10 mL)
  5. dry with materialThe combined organics were dried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customthe residue purified by column chromatography on silica eluting with 0-10% methanol/DCM

Sources & evidence

ORD record
ord-d3459a4f4e7a4e44ad0b828f51b67380
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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