Potassium Hydroxide → 3-[3-{[1-(2-{[(2R)-2-Amino-3-hydroxypropyl]oxy}phenyl)-1-methylethyl]amino}-2-oxopyrazin-1(2H)-yl]-N-cyclopropyl-4-methylbenzamide

HRID 337131Notes

Reaction equation

[CH:1]1([NH:4][C:5](=[O:38])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]([CH3:36])([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH2:29][C@H:30]4[CH2:34][O:33]C(=O)[NH:31]4)[CH3:21])[C:14]3=[O:37])[CH:7]=2)[CH2:3][CH2:2]1.[OH-].[K+]>O.CO>[NH2:31][C@H:30]([CH2:34][OH:33])[CH2:29][O:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:20]([NH:19][C:15]1[C:14](=[O:37])[N:13]([C:8]2[CH:7]=[C:6]([CH:11]=[CH:10][C:9]=2[CH3:12])[C:5]([NH:4][CH:1]2[CH2:2][CH2:3]2)=[O:38])[CH:18]=[CH:17][N:16]=1)([CH3:21])[CH3:36]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of N-cyclopropyl-4-methyl-3-[3-{[1-methyl-1-(2-{[(4S)-2-oxo-1,3-oxazolidin-4-yl]methoxy}phenyl)ethyl]amino}-2-oxopyrazin-1(2H)-yl]benzamide (Example 305a) (0.6 g) in water (10 mL) and MeOH (10 mL) was treated with potassium hydroxide (0.130 g) under nitrogen. The resulting mixture was stirred at 50° C. for 16 h. The reaction mixture was diluted with water (200 mL), and extracted with ethyl acetate (250 mL). The organic phase was dried (MgSO4), filtered and evaporated. Purification by preparative HPLC (Phenomenex Gemini column, eluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia) gave the title compound as a solid (0.105 g).

Workup

extractionextracted with ethyl acetate (250 mL)
dry with materialThe organic phase was dried (MgSO4)
filtrationfiltered
customevaporated
customPurification by preparative HPLC (Phenomenex Gemini column
washeluting with a gradient of acetonitrile in 0.2% (v/v) aqueous ammonia)

Sources & evidence

ORD record: ord-9319f4dc3ff84b1bbc2796b82a07d762
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889692B2

Reaction notes

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