Ethylenediamine → 2-[6-fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

HRID 246254Notes

Reaction equation

HRID 246254 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=4)[N:20]([CH2:28][C:29]4[CH:30]=[N:31][C:32]([N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)=[CH:33][CH:34]=4)[N:19]=3)[N:16]=2)[N:11](COCC[Si](C)(C)C)[CH:10]=1)=[O:8])[CH3:5].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=4)[N:20]([CH2:28][C:29]4[CH:30]=[N:31][C:32]([N:35]5[CH2:36][CH2:37][O:38][CH2:39][CH2:40]5)=[CH:33][CH:34]=4)[N:19]=3)[N:16]=2)[NH:11][CH:10]=1)=[O:8])[CH3:5]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712883572-[6-fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

Product 1

HCID 712884022-[6-fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amideYield 81.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[6-Fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide (50 mg, 0.074 mmol) was combined with dichloromethane (1 mL) and trifluoroacetic acid (0.17 ml, 2.22 mmol) was added. After stirring for 2 h, the reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (1 mL) and ethylenediamine (0.15 ml, 2.22 mmol) was added. After 20 min the reaction mixture was concentrated in vacuo and the residue was triturated with water (2 mL). The precipitate was filtered, washed with water and dried to afford 33 mg (77%) of 2-[6-fluoro-1-(6-morpholin-4-yl-pyridin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a light yellow solid. MS: (M+H)+=545; 1H NMR (DMSO-d6) δ: 9.14 (s, 1H), 8.52-8.60 (m, 1H), 8.45 (s, 1H), 8.31 (br. s., 1H), 8.19 (d, J=8.3 Hz, 1H), 7.89 (d, J=9.5 Hz, 1H), 7.63 (d, J=8.3 Hz, 1H), 7.16 (t, J=9.0 Hz, 1H), 6.79 (d, J=8.3 Hz, 1H), 5.63 (br. s., 2H), 4.37 (br. s., 1H), 3.65 (br. s., 4H), 3.44-3.57 (m, 2H), 3.39 (br. s., 4H), 3.27 (s, 3H), 1.30 (d, J=6.3 Hz, 3H).

Workup

  1. additionwas added
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane (1 mL)
  4. concentrationAfter 20 min the reaction mixture was concentrated in vacuo
  5. customthe residue was triturated with water (2 mL)
  6. filtrationThe precipitate was filtered
  7. washwashed with water
  8. customdried

Sources & evidence

ORD record
ord-230a71ac9ada4125968b988537ea4a8e
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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