1,2-Dichloroethane → 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methanesulfonyl-pyrrolidin-3-yl)-amide

HRID 2191568Notes

Reaction equation

HRID 2191568 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]3[C:12]([C:13]([OH:15])=O)=[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.Cl.[CH3:25][S:26]([N:29]1[CH2:33][CH2:32][CH:31]([NH2:34])[CH2:30]1)(=[O:28])=[O:27].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:25][S:26]([N:29]1[CH2:33][CH2:32][CH:31]([NH:34][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])([CH3:21])[CH3:22])[CH:11]=2)=[O:15])[CH2:30]1)(=[O:28])=[O:27]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 545939991-Methanesulfonylpyrrolidin-3-amine hydrochlorideHCID 578296532-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 670022002-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methanesulfonyl-pyrrolidin-3-yl)-amideYield 96%

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 (130 mg, 0.39 mmol), 1-methanesulfonyl-pyrrolidin-3-ylamine hydrochloride (134 mg, 0.66 mmol), EDC (82 mg, 0.43 mmol), and HOBt (58 mg, 0.43 mmol). Then added DMF (1.7 mL) followed by i-Pr2NEt (0.17 mL, 1.0 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 12 g of SiO2 using EtOAc/hexanes (gradient: 0-90% EtOAc) to afford 179 mg (96%) of 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methanesulfonyl-pyrrolidin-3-yl)-amide as a colorless oil.

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 12 g of SiO2

Sources & evidence

ORD record
ord-debd54aa4e87470d8929b8fdfdd37d2e
Source dataset
uspto-grants-2012_12
Patent number
US08329699B2

Reaction notes

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