3-[4-(azetidine-1-carbonyl)-2-chloro-phenoxy]-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide → 3-[4-(Azetidine-1-carbonyl)phenoxy]-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide

HRID 600515Notes

Reaction equation

HRID 600515 reaction equation
[N:1]1([C:5]([C:7]2[CH:37]=[CH:36][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:25]=[C:26]([O:28][C@H:29]4[CH2:33][CH2:32][N:31]([CH3:34])[C:30]4=[O:35])[CH:27]=3)[C:15]([NH:17][C:18]3[CH:23]=[N:22][C:21]([CH3:24])=[CH:20][N:19]=3)=[O:16])=[C:9](Cl)[CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1>[Pd].C1COCC1.C(O)C>[N:1]1([C:5]([C:7]2[CH:37]=[CH:36][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:25]=[C:26]([O:28][C@H:29]4[CH2:33][CH2:32][N:31]([CH3:34])[C:30]4=[O:35])[CH:27]=3)[C:15]([NH:17][C:18]3[CH:23]=[N:22][C:21]([CH3:24])=[CH:20][N:19]=3)=[O:16])=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 1

HCID 597611643-[4-(azetidine-1-carbonyl)-2-chloro-phenoxy]-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide2×

Product 1

HCID 249523053-[4-(Azetidine-1-carbonyl)phenoxy]-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamideYield 89%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-[4-(azetidine-1-carbonyl)-2-chloro-phenoxy]-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 22) (120 mg, 0.22 mmol) and 10% palladium on carbon (20 mg, catalytic) in THF (5 mL) and ethanol (5 mL) was stirred under an atmosphere of hydrogen for 16 hours. The palladium on carbon was removed by filtration and the filtrate evaporated under reduced pressure. The residue was dissolved in ethyl acetate (30 mL), washed with water (10 mL), brine (10 mL), dried (MgSO4), filtered and evaporated under reduced pressure to give product (98 mg, 89%). 1H NMR δ (300 MHz, CDCl3) 2.12-2.26 (m, 1H), 2.36 (quintet, 2H), 2.52-2.67 (m, 4H), 2.94 (s, 3H), 3.35-3.57 (m, 2H), 4.19-4.42 (m, 4H), 4.93 (t, 1H), 6.93 (s, 1H), 7.03 (d, 2H), 7.20 (s, 1H), 7.42 (s, 1H), 7.66 (d, 2H), 8.15 (s, 1H), 8.54 (s, 1H), 9.52 (s, 1H); m/z 502 (M+H)+.

Workup

  1. customThe palladium on carbon was removed by filtration
  2. customthe filtrate evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (30 mL)
  4. washwashed with water (10 mL), brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-ebb04fe4185e4489b87ab967fd899071
Source dataset
uspto-grants-2011_03
Patent number
US07902200B2

Reaction notes

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