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 2070808Notes

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-a94c44db929a43b5936c5ed4dc62cc20
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299246B2

Reaction notes

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