Ethylenediamine → 2-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 246248Notes

Reaction equation

HRID 246248 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7](=[O:45])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH2:32][CH2:33][N:34]([CH3:36])[CH3:35])[N:23]=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:4]1)#[N:2].C(O)(C(F)(F)F)=O.C(N)CN>C(Cl)Cl>[C:1]([CH:3]1[CH2:4][N:5]([C:7](=[O:45])[C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH2:32][CH2:33][N:34]([CH3:36])[CH3:35])[N:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:6]1)#[N:2]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712890492-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Product 1

HCID 712887462-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amideYield 67.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 10 mL pear-shaped flask, 2-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (130 mg, 0.20 mmol) was combined with CH2Cl2 (1 ml) to give a yellow solution. TFA (0.24 ml, 3.2 mmol) was added and the reaction was stirred at room temperature for 2 h. The crude reaction mixture was concentrated in vacuo and redissolved in CH2Cl2. Ethylenediamine (0.33 ml, 5.0 mmol) was added dropwise and the reaction was stirred at room temperature for 20 min. The crude reaction mixture was concentrated in vacuo. The residue was suspended in cold water and filtered, washing with water then dried on high vacuum to give 70 mg (64%) of 2-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a yellow solid. MS: (M+H)+=520; 1H NMR (DMSO-d6) δ: 9.14 (s, 1H), 8.70 (d, J=7.0 Hz, 1H), 8.36-8.63 (m, 2H), 8.03 (s, 1H), 7.25 (d, J=6.6 Hz, 1H), 4.48-4.82 (m, 5H), 4.16-4.34 (m, 1H), 4.01-4.15 (m, 1H), 3.86 (d, J=5.1 Hz, 1H), 3.33 (br. s., 1H), 2.80 (t, J=6.1 Hz, 2H), 2.20 (s, 6H), 1.40 (t, J=6.4 Hz, 3H).

Workup

  1. customto give a yellow solution
  2. customThe crude reaction mixture
  3. concentrationwas concentrated in vacuo
  4. dissolutionredissolved in CH2Cl2
  5. stirringthe reaction was stirred at room temperature for 20 min
  6. customThe crude reaction mixture
  7. concentrationwas concentrated in vacuo
  8. filtrationfiltered
  9. washwashing with water
  10. customthen dried on high vacuum

Sources & evidence

ORD record
ord-cf8f7e53bb604959918f666996915af6
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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