Ethylenediamine → (6-Chloro-3-{7-[(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-5H-pyrrolo[2,3-b]pyrazin-2-yl}-indazol-1-yl)-acetic acid

HRID 246246Notes

Reaction equation

HRID 246246 reaction equation
C([O:5][C:6](=[O:48])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:17])[CH:15]=2)[C:10]([C:18]2[N:19]=[C:20]3[C:26]([C:27](=[O:39])[NH:28][C@H:29]([CH3:38])[C:30]([N:32]4[CH2:35][CH:34]([C:36]#[N:37])[CH2:33]4)=[O:31])=[CH:25][N:24](COCC[Si](C)(C)C)[C:21]3=[N:22][CH:23]=2)=[N:9]1)(C)(C)C.C(O)(C(F)(F)F)=O.C(N)CN>C(Cl)Cl>[Cl:17][C:14]1[CH:15]=[C:16]2[C:11]([C:10]([C:18]3[N:19]=[C:20]4[C:26]([C:27](=[O:39])[NH:28][C@H:29]([CH3:38])[C:30]([N:32]5[CH2:35][CH:34]([C:36]#[N:37])[CH2:33]5)=[O:31])=[CH:25][NH:24][C:21]4=[N:22][CH:23]=3)=[N:9][N:8]2[CH2:7][C:6]([OH:48])=[O:5])=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71279425{6-Chloro-3-[7-[(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-acetic acid tert-butyl ester

Product 1

HCID 71280559(6-Chloro-3-{7-[(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-5H-pyrrolo[2,3-b]pyrazin-2-yl}-indazol-1-yl)-acetic acidYield 36.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 5 mL pear-shaped flask, {6-chloro-3-[7-[(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-acetic acid tert-butyl ester (30 mg, 0.043 mmol) was combined with CH2Cl2 (1 ml) to give a light yellow solution. TFA (0.10 ml, 1.3 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 (88 μl, 1.3 mmol) was added dropwise and the reaction was stirred at room temperature for 30 min. The crude reaction mixture was concentrated in vacuo. The residue was dissolved in water and it was lyophilized overnight. The yellow waxy solid was suspended in water and filtered, washing with water then dried on high vacuum to give 8 mg (32%) of (6-Chloro-3-{7-[(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-5H-pyrrolo[2,3-b]pyrazin-2-yl}-indazol-1-yl)-acetic acid as a yellow solid. MS: (M+H)+=507.

Workup

  1. customto give a light 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 30 min
  6. customThe crude reaction mixture
  7. concentrationwas concentrated in vacuo
  8. dissolutionThe residue was dissolved in water
  9. waitit was lyophilized overnight
  10. filtrationfiltered
  11. washwashing with water
  12. customthen dried on high vacuum

Sources & evidence

ORD record
ord-c71ffa6e3b4345208930a895e4faf06c
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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