O-Methylhydroxylamine hydrochloride → N-Methoxy-4-methyl-3-[3-[[(1R,2S)-2-methyl-1-(1-naphthalenyl)-3-(1-pyrrolidinyl)propyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide

HRID 1697313Notes

Reaction equation

HRID 1697313 reaction equation
C([Mg]Cl)(C)C.[CH3:6][C:7]1[CH:16]=[CH:15][C:10]([C:11](OC)=[O:12])=[CH:9][C:8]=1[N:17]1[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C@@H:24]([C:33]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH:36]=[CH:35][CH:34]=2)[C@@H:25]([CH3:32])[CH2:26][N:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:18]1=[O:43].Cl.[CH3:45][O:46][NH2:47]>O1CCCC1>[CH3:45][O:46][NH:47][C:11](=[O:12])[C:10]1[CH:15]=[CH:16][C:7]([CH3:6])=[C:8]([N:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C@@H:24]([C:33]3[C:42]4[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=4)[CH:36]=[CH:35][CH:34]=3)[C@@H:25]([CH3:32])[CH2:26][N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[C:18]2=[O:43])[CH:9]=1

Participants

5

Reactant 3

HCID 521874O-Methylhydroxylamine hydrochlorideHCID 86663244HCID 86663244, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 86663243N-Methoxy-4-methyl-3-[3-[[(1R,2S)-2-methyl-1-(1-naphthalenyl)-3-(1-pyrrolidinyl)propyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamideYield 70.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of iso-propylmagnesium chloride (2M in diethyl ether, 1.2 mL) was added dropwise to a stirred mixture of 4-methyl-3-[3-[[(1R,2S)-2-methyl-1-(1-naphthalenyl)-3-(1-pyrrolidinyl)propyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzoic acid, methyl ester (Example 158b, 90 mg), O-methylhydroxylamine hydrochloride (65 mg) and tetrahydrofuran (2 mL) at room temperature. After 15 min the reaction was quenched with sat. aqueous NH4Cl and extracted into ethyl acetate. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound as a solid (65 mg).

Workup

  1. customAfter 15 min the reaction was quenched with sat. aqueous NH4Cl
  2. extractionextracted into ethyl acetate
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Sources & evidence

ORD record
ord-df1c69737ef14499b576195c389394d7
Source dataset
uspto-grants-2012_04
Patent number
US08163905B2

Reaction notes

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