Ethylenediamine → HCID 178481763, compound

HRID 246787Notes

Reaction equation

HRID 246787 reaction equation
[OH:1][C@H:2]1[CH2:5][C@H:4]([NH:6][C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[C:26]5[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=5)[N:20]([CH3:28])[N:19]=4)[N:16]=3)[N:11](COCC[Si](C)(C)C)[CH:10]=2)=[O:8])[CH2:3]1.FC(F)(F)C(O)=O.C(N)CN>ClCCl.O.C(OCC)(=O)C>[OH:1][C@H:2]1[CH2:3][C@H:4]([NH:6][C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[C:26]5[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=5)[N:20]([CH3:28])[N:19]=4)[N:16]=3)[NH:11][CH:10]=2)=[O:8])[CH2:5]1

Participants

7

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 178481751HCID 178481751, compound

Product 1

HCID 178481763HCID 178481763, compoundYield 72.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-hydroxy-cyclobutyl)-amide (100 mg, 0.20 mmol) was dissolved in dichloromethane (1.0 mL). Trifluoroacetic acid (0.61 mL, 7.92 mmol) was added and the orange solution was stirred at room temperature for 2 h. The reaction mixture was concentrated. The residue (light orange foam) was suspended in dichloromethane (1.0 mL) and ethylenediamine (0.80 ml, 11.8 mmol) was added. The light yellow suspension was stirred at room temperature for 1 h. The reaction mixture was diluted with water and ethyl acetate. The suspension was filtered and washed with water (hot) and ethyl acetate. The resulting off-white powder was dried under high vacuum to provide 55 mg (66%; purity=90%) 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-hydroxycyclobutyl)-amide. LC/MS: [M−H]−=379. 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 12.31-12.64 (br. s., 1H), 9.10 (s, 1H), 8.52 (dd, J=9.0, 5.2 Hz, 1H), 8.43 (s, 1H), 8.36 (d, J=7.1 Hz, 1H), 7.72 (dd, J=9.7, 2.1 Hz, 1H), 7.20 (td, J=9.1, 2.3 Hz, 1H), 5.19-5.26 (m, 1H), 4.52-4.61 (m, 1H), 4.44-4.61 (m, 1H), 4.16 (s, 3H), 2.25-2.40 (m, 4H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. stirringThe light yellow suspension was stirred at room temperature for 1 h
  3. filtrationThe suspension was filtered
  4. washwashed with water (hot) and ethyl acetate
  5. customThe resulting off-white powder was dried under high vacuum

Sources & evidence

ORD record
ord-0e1f3160c9be430c86a7e830ba88bff5
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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