Ethylenediamine → HCID 71285810, compound

HRID 246153Notes

Reaction equation

HRID 246153 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([NH:7][C:8]([C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([C:19]3[C:27]4[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=4)[N:21]([CH3:29])[N:20]=3)[N:17]=2)[N:12](COCC[Si](C)(C)C)[CH:11]=1)=[O:9])[CH2:5][CH3:6].C(O)(C(F)(F)F)=O.C(N)CN>ClCCl>[CH3:1][O:2][CH2:3][C@H:4]([NH:7][C:8]([C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([C:19]3[C:27]4[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=4)[N:21]([CH3:29])[N:20]=3)[N:17]=2)[NH:12][CH:11]=1)=[O:9])[CH2:5][CH3:6]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71288294HCID 71288294, compound

Product 1

HCID 71285810HCID 71285810, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a sealed 25 mL round-bottom flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methoxymethyl-propyl)-amide (40 mg, 0.074 mmol) and TFA (0.9 ml, 11.7 mmol) were combined with dichloromethane (3 ml) to give an orange solution. The reaction mixture was stirred at room temperature for 2.5 h. The reaction mixture was then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (3 mL) and ethylenediamine (500 μl, 7.4 mmol) was added. The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated and the residue was precipitated with water. The suspension was stirred for 1 h and the crude solid collected by filtration. The crude solid was purified by trituration (11:1:1 hot heptane/dichloromethane/EtOAc) to afford 21 mg (69%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methoxymethyl-propyl)-amide as an off-white solid. MS: [M+H]+=413; 1H NMR (DMSO-d6) δ: 12.84 (br. s., 1H), 9.12 (s, 1H), 8.51 (d, J=8.7 Hz, 1H), 8.45 (s, 1H), 8.17 (d, J=9.1 Hz, 1H), 8.01 (d, J=1.5 Hz, 1H), 7.25 (dd, J=8.7, 1.5 Hz, 1H), 4.16-4.27 (m, 1H), 4.18 (s, 3H), 3.57 (dd, J=9.6, 4.3 Hz, 1H), 3.47 (dd, J=9.6, 4.3 Hz, 1H), 3.27 (s, 3H), 1.71-1.89 (m, 1H), 1.47-1.71 (m, 1H), 0.96 (t, J=7.4 Hz, 3H).

Workup

  1. customto give an orange solution
  2. concentrationThe reaction mixture was then concentrated under reduced pressure
  3. dissolutionThe resultant crude solid was dissolved in dichloromethane (3 mL)
  4. stirringThe reaction mixture was stirred at room temperature for 18 h
  5. concentrationThe reaction mixture was concentrated
  6. customthe residue was precipitated with water
  7. stirringThe suspension was stirred for 1 h
  8. filtrationthe crude solid collected by filtration
  9. customThe crude solid was purified by trituration (11:1:1 hot heptane/dichloromethane/EtOAc)

Sources & evidence

ORD record
ord-23a8d79ae866463295e1152b8e8ed1b2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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