Ethylenediamine → HCID 178481760, compound

HRID 246139Notes

Reaction equation

HRID 246139 reaction equation
[OH: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>[OH: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 acid2×HCID 178481748HCID 178481748, compound

Product 1

HCID 178481760HCID 178481760, compoundYield 61%

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 (trans-4-hydroxycyclohexyl)amide (60 mg, 0.108 mmol) was dissolved in dichloromethane (3 mL). Trifluoroacetic acid (0.2 mL, 2.6 mmol) was added and the orange reaction mixture was stirred at room temperature for 15 h. Additional trifluoroacetic acid (0.7 mL) was added and the reaction stirred for an additional 5 h. The reaction mixture was then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (3 mL) and ethylenediamine (0.20 mL, 2.96 mmol) was added. The light yellow reaction mixture was stirred at room temperature for 20 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 28 mg (60%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-4-hydroxy-cyclohexyl)amide as a light yellow solid. MS: [M+H]+=525; 1H NMR (300 MHz, DMSO-d6) δ: 9.08 (s, 2H), 8.40 (s, 1H), 8.43 (d, J=1.0 Hz, 1H), 8.02 (d, J=1.0 Hz, 1H), 8.01 (s, 1H), 7.28 (dd, J=8.6, 2.0 Hz, 1H), 4.45-4.76 (m, 1H), 4.17 (s, 3H), 3.70-3.96 (m, 1H), 3.43-3.59 (m, 1H), 2.07 (d, J=11.1 Hz, 2H), 1.92 (d, J=10.6 Hz, 2H), 1.18-1.55 (m, 4H).

Workup

  1. stirringthe reaction stirred for an additional 5 h
  2. concentrationThe reaction mixture was then concentrated under reduced pressure
  3. dissolutionThe resultant crude solid was dissolved in dichloromethane (3 mL)
  4. stirringThe light yellow reaction mixture was stirred at room temperature for 20 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. washThe crude solid was sequentially washed with water, dichloromethane, ethyl acetate, and hexanes

Sources & evidence

ORD record
ord-2a06fe13b7244b0db234b02f683d2f3e
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…