Ethylenediamine → HCID 71288925, compound

HRID 246147Notes

Reaction equation

HRID 246147 reaction equation
[C:1]([C@H:3]1[CH2:8][CH2:7][CH2:6][C@H:5]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=5)[N:23]([CH3:31])[N:22]=4)[N:19]=3)[N:14](COCC[Si](C)(C)C)[CH:13]=2)=[O:11])[CH2:4]1)#[N:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([C@H:3]1[CH2:8][CH2:7][CH2:6][C@H:5]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=5)[N:23]([CH3:31])[N:22]=4)[N:19]=3)[NH:14][CH:13]=2)=[O:11])[CH2:4]1)#[N:2]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71288927HCID 71288927, compound

Product 1

HCID 71288925HCID 71288925, compoundYield 95%

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-3-cyanocyclohexyl)-amide (48 mg, 0.085 mmol) was dissolved in dichloromethane (3 mL). Trifluoroacetic acid (1.2 mL, 15.6 mmol) was added and the orange reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (3 mL) and ethylenediamine (0.50 mL, 7.4 mmol) was added. The light yellow 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 sequentially washed with water, ethyl acetate, and hexanes to afford 35 mg (95%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-cyanocyclohexyl)-amide as an off-white solid. MS: [M+Na]+=474; 1H NMR (DMSO-d6) δ: 12.79 (br. s., 1H), 9.08 (s, 1H), 8.46 (s, 1H), 8.40 (d, J=8.7 Hz, 1H), 8.08 (d, J=7.9 Hz, 1H), 8.00 (d, J=0.8 Hz, 1H), 7.37 (dd, J=8.5, 1.1 Hz, 1H), 4.17 (s, 3H), 4.01-4.31 (m, 1H), 3.30-3.49 (m, 1H), 2.24 (d, J=13.2 Hz, 1H), 2.07 (d, J=12.1 Hz, 1H), 1.59-1.94 (m, 5H), 1.36-1.59 (m, 1H).

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. dissolutionThe resultant crude solid was dissolved in dichloromethane (3 mL)
  3. stirringThe light yellow reaction mixture was stirred at room temperature for 18 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, ethyl acetate, and hexanes

Sources & evidence

ORD record
ord-80120edcf54049e290f92d52cbe7d81f
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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