Ethylenediamine → HCID 71285906, compound

HRID 246193Notes

Reaction equation

HRID 246193 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]([NH:11][C:12]([C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([C:23]3[C:31]4[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=4)[N:25]([CH3:33])[N:24]=3)[N:21]=2)[N:16](COCC[Si](C)(C)C)[CH:15]=1)=[O:13])[CH2:5][CH2:6][S:7]([CH3:10])(=[O:9])=[O:8].C(O)(C(F)(F)F)=O.C(N)CN>ClCCl>[CH3:10][S:7]([CH2:6][CH2:5][C@H:4]([NH:11][C:12]([C:14]1[C:22]2[C:17](=[N:18][CH:19]=[C:20]([C:23]3[C:31]4[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=4)[N:25]([CH3:33])[N:24]=3)[N:21]=2)[NH:16][CH:15]=1)=[O:13])[CH2:3][O:2][CH3:1])(=[O:8])=[O:9]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71285981HCID 71285981, compound

Product 1

HCID 71285906HCID 71285906, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 10 mL round-bottom flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-1-methoxymethyl-3-methanesulfonyl-propyl)-amide (35 mg, 0.058 mmol) and TFA (0.5 ml, 6.5 mmol) were combined with dichloromethane (1.5 ml) to give an orange solution. The reaction mixture was stirred at room temperature for 2.5 h then concentrated under reduced pressure. The resultant crude solid was dissolved in dichloromethane (1 mL) and ethylenediamine (0.19 ml, 2.8 mmol) was added. The reaction mixture was stirred at room temperature for 18 h then 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 (dichloromethane/heptane) to afford 12 mg (44%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-3-methanesulfonyl-1-methoxymethyl-propyl)-amide as a light yellow solid. MS: [M+Na]+=497; 1H NMR (300 MHz, DMSO-d6) δ: 12.87 (br. s., 1H), 9.12 (s, 1H), 8.54 (dd, J=8.7, 5.3 Hz, 1H), 8.47 (s, 1H), 8.28 (d, J=9.1 Hz, 1H), 7.69 (dd, J=9.8, 2.3 Hz, 1H), 7.19 (td, J=9.1, 2.3 Hz, 1H), 4.35-4.55 (m, 1H), 4.15 (s, 3H), 3.60 (dd, J=9.8, 4.2 Hz, 1H), 3.51 (dd, J=9.4, 4.2 Hz, 1H), 3.26 (s, 3H), 3.20-3.28 (m, 2H), 2.97 (s, 3H), 2.02-2.23 (m, 2H).

Workup

  1. customto give an orange solution
  2. concentrationthen concentrated under reduced pressure
  3. dissolutionThe resultant crude solid was dissolved in dichloromethane (1 mL)
  4. stirringThe reaction mixture was stirred at room temperature for 18 h
  5. concentrationthen 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 (dichloromethane/heptane)

Sources & evidence

ORD record
ord-eb0d24ca7c034331b100c781af6ff65b
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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