Ethylenediamine → HCID 178481758, compound

HRID 246141Notes

Reaction equation

HRID 246141 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[C:28]5[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=5)[N:22]([CH3:30])[N:21]=4)[N:18]=3)[N:13](COCC[Si](C)(C)C)[CH:12]=2)=[O:10])[CH2:4][CH2:3]1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[C:28]5[C:23](=[CH:24][C:25]([Cl:29])=[CH:26][CH:27]=5)[N:22]([CH3:30])[N:21]=4)[N:18]=3)[NH:13][CH:12]=2)=[O:10])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 178481747HCID 178481747, compound

Product 1

HCID 178481758HCID 178481758, compoundYield 94.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 25 mL round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-4-aminocyclohexyl)amide (85 mg, 0.153 mmol) was dissolved in dichloromethane (8 mL). Trifluoroacetic acid (2.5 mL, 32.4 mmol) was added and the orange reaction mixture was stirred at room temperature for 3 h. The reaction mixture was then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (8 mL) and ethylenediamine (1 mL, 14.8 mmol) was added. The reaction mixture was stirred at room temperature for 2 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 sequentially washed with water, dichloromethane, ethyl acetate, and hexanes to afford 61 mg (93%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-4-aminocyclohexyl)-amide as a light yellow solid. MS: [M+H]+=424; 1H NMR (300 MHz, DMSO-d6) δ: 9.05 (d, J=1.0 Hz, 1H), 8.47 (d, J=9.1 Hz, 1H), 8.42 (d, J=1.0 Hz, 1H), 8.08 (d, J=7.1 Hz, 1H), 7.98 (s, 1H), 7.40 (d, J=9.1 Hz, 1H), 4.17 (d, J=1.0 Hz, 3H), 4.00 (br. s., 1H), 2.96 (br. s., 1H), 1.87-2.02 (m, 2H), 1.66-1.76 (m, 2H), 1.55-1.66 (m, 2H), 1.44-1.54 (m, 2H).

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. dissolutionThe resultant crude solid was dissolved in dichloromethane (8 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 2 h
  4. concentrationThe reaction mixture was concentrated
  5. customthe residue was precipitated with water
  6. stirringThe suspension was stirred for 1 h
  7. filtrationthe crude solid collected by filtration
  8. washThe crude solid was sequentially washed with water, dichloromethane, ethyl acetate, and hexanes

Sources & evidence

ORD record
ord-f103585df9c34f03b31af2ead20206a4
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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