1,2-Dichloroethane → 3-{[2-Cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

HRID 2191563Notes

Reaction equation

HRID 2191563 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13](O)=[O:14])=[CH:11][N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:7]3=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[CH3:24][O:25][C:26]([C:28]1([NH2:40])[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29]1)=[O:27].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:24][O:25][C:26]([C:28]1([NH:40][C:13]([C:12]2[C:6]3[C:7](=[N:8][CH:9]=[C:4]([CH:1]4[CH2:2][CH2:3]4)[N:5]=3)[N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:11]=2)=[O:14])[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])[CH2:29]1)=[O:27]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 576862811-Tert-butyl 3-methyl 3-aminopyrrolidine-1,3-dicarboxylateHCID 578296532-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 585252753-{[2-Cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl esterYield 91.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a round-bottomed flask were combined 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (180 mg, 0.54 mmol), 3-amino-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (214 mg, 0.87 mmol), EDC (114 mg, 0.59 mmol), and HOBt (80 mg, 0.59 mmol). Then added DMF (2.4 mL) followed by i-Pr2NEt (0.14 mL, 0.80 mmol). The reaction mixture was stirred at room temperature overnight then quenched with H2O and extracted with Et2O (2×). The combined organics were washed with H2O (2×) and brine then dried over Na2SO4 and concentrated. The residue was purified by chromatography over 24 g of SiO2 using EtOAc/hexanes (gradient: 0-40% EtOAc) to afford 276 mg (91%) of 3-{[2-Cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester as an off-white foam.

Workup

  1. customIn a round-bottomed flask were combined
  2. customthen quenched with H2O
  3. extractionextracted with Et2O (2×)
  4. washThe combined organics were washed with H2O (2×) and brine
  5. dry with materialthen dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography over 24 g of SiO2

Sources & evidence

ORD record
ord-dc41c4543fc94ac38c9f5c90bd36bf27
Source dataset
uspto-grants-2012_12
Patent number
US08329699B2

Reaction notes

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