Cyclopropylamine → N-Cyclopropyl-3-[3-[[(1R,2R)-3-hydroxy-2-methyl-1-phenylpropyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzamide

HRID 1697311Notes

Reaction equation

HRID 1697311 reaction equation
C([Mg]Cl)(C)C.[OH:6][CH2:7][C@H:8]([CH3:35])[C@@H:9]([NH:16][C:17]1[C:18](=[O:34])[N:19]([C:23]2[CH:24]=[C:25]([CH:30]=[CH:31][C:32]=2[CH3:33])[C:26]([O:28]C)=O)[CH:20]=[CH:21][N:22]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH:36]1([NH2:39])[CH2:38][CH2:37]1>O1CCCC1>[CH:36]1([NH:39][C:26](=[O:28])[C:25]2[CH:30]=[CH:31][C:32]([CH3:33])=[C:23]([N:19]3[CH:20]=[CH:21][N:22]=[C:17]([NH:16][C@@H:9]([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=4)[C@@H:8]([CH3:35])[CH2:7][OH:6])[C:18]3=[O:34])[CH:24]=2)[CH2:38][CH2:37]1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 866632413-[3-[[(1R,2R)-3-hydroxy-2-methyl-1-phenylpropyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid, methyl esterHCID 178418918HCID 178418918, compound

Product 1

HCID 66685987N-Cyclopropyl-3-[3-[[(1R,2R)-3-hydroxy-2-methyl-1-phenylpropyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of iso-propylmagnesium chloride (2M in tetrahydrofuran, 5.5 mL) was added dropwise to a stirred mixture of 3-[3-[[(1R,2R)-3-hydroxy-2-methyl-1-phenylpropyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid, methyl ester (Example 136c, 500 mg), cyclopropylamine (0.3 mL) and tetrahydrofuran (20 mL) at 0° C. 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 to give a crude title product (525 mg). Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound.

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. customto give a crude title product (525 mg)
  7. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Sources & evidence

ORD record
ord-c3be4bcbe05640ddb05d656bf801f0d9
Source dataset
uspto-grants-2012_04
Patent number
US08163905B2

Reaction notes

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