Ethylenediamine → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methanesulfonyl-piperidin-3-yl)-amide

HRID 245828Notes

Reaction equation

HRID 245828 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][CH2:8][C@@H:7]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[N:16](COCC[Si](C)(C)C)[CH:15]=2)=[O:13])[CH2:6]1)(=[O:4])=[O:3].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][CH2:8][C@@H:7]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([Cl:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[NH:16][CH:15]=2)=[O:13])[CH2:6]1)(=[O:3])=[O:4]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712881522-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methanesulfonyl-piperidin-3-yl)-amide

Product 1

HCID 712860502-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methanesulfonyl-piperidin-3-yl)-amideYield 66.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methanesulfonyl-piperidin-3-yl)-amide (103 mg, 0.167 mmol) was dissolved in dichloromethane (0.8 ml) and trifluoroacetic acid (0.5 ml, 6.6 mmol) was added. The reaction mixture was stirred at room temperature for 2.5 h then concentrated. The residue was dissolved in dichloromethane (0.8 ml) and ethylenediamine (0.67 ml, 9.92 mmol) was added. The resultant light yellow suspension was stirred at room temperature for 45 min then quenched with water and diluted with ethyl acetate. The suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 54 mg (63%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methanesulfonyl-piperidin-3-yl)-amide as a light yellow powder. MS: (M+H)+=488; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.06 (s, 1H), 8.47 (s, 1H), 8.41 (d, J=8.7 Hz, 1H), 8.13 (d, J=7.6 Hz, 1H), 8.00 (s, 1H), 7.36 (d, J=8.7 Hz, 1H), 4.17 (s, 3H), 4.06-4.15 (m, 1H), 3.66-3.75 (m, 1H), 3.34-3.41 (m, 1H), 2.89-2.99 (m, 1H), 2.86 (s, 3H), 2.80 (d, J=10.6 Hz, 1H), 2.11 (br. s., 1H), 1.87 (br. s., 1H), 1.51-1.74 (m, 2H)

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.8 ml)
  3. stirringThe resultant light yellow suspension was stirred at room temperature for 45 min
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-2a54dd110cc0433d810e64000344109d
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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