Ethylenediamine → HCID 131731219, compound

HRID 246007Notes

Reaction equation

HRID 246007 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:40])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19](C4C5C(=CC=CC=5)C=CN=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].C(O)(C(F)(F)F)=O.C(N)CN>C(Cl)Cl>[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:40])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712889362-isoquinolin-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Product 1

HCID 131731219HCID 131731219, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-isoquinolin-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (52 mg, 0.094 mmol) in CH2Cl2 (2 mL) was added TFA (1 mL, 13.0 mmol). The reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was redissolved in CH2Cl2 (2 mL) and ethylene diamine (0.4 mL, 6.0 mmol) was added. The reaction mixture was stirred for 1 h then quenched with water and extracted with CH2Cl2. The combined organics were concentrated and the residue was purified by silica gel chromatography with 0% to 5% MeOH/CH2Cl2 (0.5% NH4OH) to afford 17 mg (43%) of 2-isoquinolin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as an off-white solid. MS (M+H)+=426; mp=180-185° C.; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 13.02 (br. s., 1H), 9.09 (s, 1H), 8.91 (d, J=8.7 Hz, 1H), 8.68 (d, J=5.7 Hz, 1H), 8.55 (d, J=9.1 Hz, 1H), 8.44 (d, J=7.6 Hz, 1H), 8.09 (d, J=7.9 Hz, 1H), 7.98 (d, J=5.7 Hz, 1H), 7.84 (t, J=7.6 Hz, 1H), 7.66-7.77 (m, 1H), 4.40-4.70 (m, 3H), 4.12 (q, J=9.7 Hz, 1H), 3.93-4.04 (m, 1H), 3.74-3.88 (m, 1H), 1.22 (t, J=6.6 Hz, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in CH2Cl2 (2 mL)
  3. stirringThe reaction mixture was stirred for 1 h
  4. customthen quenched with water
  5. extractionextracted with CH2Cl2
  6. concentrationThe combined organics were concentrated
  7. customthe residue was purified by silica gel chromatography with 0% to 5% MeOH/CH2Cl2 (0.5% NH4OH)

Sources & evidence

ORD record
ord-1879210d5e224ddf8dd42d42e1dfc2b7
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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