Diisopropylethylamine → 3-Methoxymethyl-1-{2-oxo-2-[4-(4-pyrimidin-2-yl-phenyl)-piperazin-1-yl]-ethyl}-pyrrolidine-3-carboxylic acid methyl ester

HRID 1038022Notes

Reaction equation

HRID 1038022 reaction equation
[CH3:1][O:2][C:3]([C:5]1([CH2:14][O:15][CH3:16])[CH2:9][CH2:8][N:7]([CH2:10][C:11]([OH:13])=O)[CH2:6]1)=[O:4].[N:17]1([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[N:34]=[CH:33][CH:32]=[CH:31][N:30]=3)=[CH:25][CH:24]=2)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1([CH2:14][O:15][CH3:16])[CH2:9][CH2:8][N:7]([CH2:10][C:11](=[O:13])[N:20]2[CH2:21][CH2:22][N:17]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[N:30]=[CH:31][CH:32]=[CH:33][N:34]=4)=[CH:25][CH:24]=3)[CH2:18][CH2:19]2)[CH2:6]1)=[O:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 534203192-(4-(Piperazin-1-yl)phenyl)pyrimidine2×HCID 595113811-Carboxymethyl-3-methoxymethyl-pyrrolidine-3-carboxylic acid methyl ester2×

Product 1

HCID 595113513-Methoxymethyl-1-{2-oxo-2-[4-(4-pyrimidin-2-yl-phenyl)-piperazin-1-yl]-ethyl}-pyrrolidine-3-carboxylic acid methyl esterYield 101.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-carboxymethyl-3-methoxymethyl-pyrrolidine-3-carboxylic acid methyl ester (compound 97) (0.21 mmol), 2-(4-piperazin-1-yl-phenyl)-pyrimidine (compound 10, see Example 1 Step 7) (0.21 mmol), O-(7-azabenzotriazol-1-yl-)-N,N,N′, N′-tetramethyluronium hexafluorophosphate (HATU) (78 mg, 0.21 mmol) in dry DMF (2 ml) was added N,N-diisopropylethylamine (108 μl, 0.62 mmol). The reaction mixture was stirred for 4 hours, and evaporated to a residue that was partitioned in ethyl acetate and saturated sodium carbonate. Organic layer was isolated, washed with water, brine and dried over magnesium sulfate. Evaporation of solvent provided a crude product which was chromatographed with 5% methanol in dichloromethane to furnish the title compound (97 mg).

Workup

  1. customevaporated to a residue that
  2. customwas partitioned in ethyl acetate
  3. customOrganic layer was isolated
  4. washwashed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. customEvaporation of solvent
  7. customprovided a crude product which
  8. customwas chromatographed with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-7ead6cd399e64d2abe3d37a9057d8270
Source dataset
uspto-grants-2013_10
Patent number
US08546404B2

Reaction notes

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