1,2-Dichloroethane → 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-cyano-1-cyclopropyl-2,2-dimethyl-ethyl)-amide

HRID 446936Notes

Reaction equation

HRID 446936 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.Cl.[NH2:25][CH:26]([CH:32]1[CH2:34][CH2:33]1)[C:27]([CH3:31])([CH3:30])[C:28]#[N:29].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:28]([C:27]([CH3:31])([CH3:30])[CH:26]([NH:25][C:13]([C:12]1[C:6]2[C:7](=[N:8][CH:9]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[N:5]=2)[N:10]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:21])[CH3:22])[CH:11]=1)=[O:14])[CH:32]1[CH2:34][CH2:33]1)#[N:29]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 575165883-Amino-3-cyclopropyl-2,2-dimethylpropanenitrile hydrochlorideHCID 578296532-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Product 1

HCID 670092382-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-cyano-1-cyclopropyl-2,2-dimethyl-ethyl)-amideYield 74.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a flask were combined 2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (120 mg, 0.36 mmol), 3-amino-3-cyclopropyl-2,2-dimethyl-propionitrile hydrochloride (75 mg, 0.43 mmol), HOBt (54 mg, 0.40 mmol), and EDC (77 mg, 0.40 mmol). Then added DMF (2 mL) followed by diisopropylethylamine (0.16 mL, 0.90 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (3×). The combined organics were washed with water (3×) then dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (30% to 50% EtOAc/hexanes) to afford 121 mg (74%) of 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-cyano-1-cyclopropyl-2,2-dimethyl-ethyl)-amide as an off-white foam.

Workup

  1. customIn a flask were combined
  2. customthen quenched with water
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organics were washed with water (3×)
  5. dry with materialthen dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by SiO2 chromatography (30% to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-fc372240225c45e9a8f98563d1ebfe13
Source dataset
uspto-grants-2013_07
Patent number
US08481541B2

Reaction notes

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