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

HRID 245811Notes

Reaction equation

HRID 245811 reaction equation
[OH:1][C:2]([CH3:37])([CH3:36])[C@H:3]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])[CH3:4].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[OH:1][C:2]([CH3:36])([CH3:37])[C@H:3]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712860372-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-amide

Product 1

HCID 712882362-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-amideYield 58.3%

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)-2-hydroxy-1,2-dimethyl-propyl)-amide (121 mg, 0.22 mmol) was dissolved in dichloromethane (1 ml) and trifluoroacetic acid (0.7 ml, 9.0 mmol) was added. The reaction mixture was stirred at room temperature for 2.5 h then concentrated. The residue was redissolved in dichloromethane (1 ml) and ethylenediamine (0.9 ml, 13.3 mmol) was added. The solution was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resultant suspension was filtered, rinsed with hot water and ethyl acetate then dried under high vacuum to provide 53 mg (58%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-amide as an off-white powder. MS: (M+H)+=413; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.83 (br. s., 1H), 9.14 (s, 1H), 8.75 (d, J=8.7 Hz, 1H), 8.42 (s, 1H), 8.16 (d, J=9.4 Hz, 1H), 7.95 (d, J=1.1 Hz, 1H), 7.36 (dd, J=8.7, 1.1 Hz, 1H), 4.78 (s, 1H), 4.17 (s, 3H), 4.03-4.16 (m, 1H), 1.22-1.28 (m, 6H), 1.16 (s, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was redissolved in dichloromethane (1 ml)
  3. stirringThe solution was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resultant suspension was filtered
  7. washrinsed with hot water and ethyl acetate
  8. customthen dried under high vacuum

Sources & evidence

ORD record
ord-ffc81a7c251347b0b850d6aba58c9124
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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