Ethylenediamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-amide

HRID 245926Notes

Reaction equation

HRID 245926 reaction equation
[F:1][CH:2]1[CH2:5][N:4]([C:6]([C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[N:17](COCC[Si](C)(C)C)[CH:16]=2)=[O:14])[CH2:9][CH2:10][CH3:11])=[O:7])[CH2:3]1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[F:1][CH:2]1[CH2:5][N:4]([C:6]([C@H:8]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[NH:17][CH:16]=2)=[O:14])[CH2:9][CH2:10][CH3:11])=[O:7])[CH2:3]1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712882122-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-amide

Product 1

HCID 712859402-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-amideYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-amide (126 mg, 0.21 mmol) was dissolved in dichloromethane (1.1 ml) and trifluoroacetic acid (0.65 ml, 8.4 mmol) was added. The reaction mixture was stirred at room temperature for 2.5 h then concentrated. The residue was dissolved in dichloromethane (1.1 ml) and ethylenediamine (0.85 ml, 12.7 mmol) was added. The reaction was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resulting suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 49 mg (50%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-amide as an off-white powder. MS: (M+H)+=468; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.84 (br. s, 1H), 9.15 (s, 1H), 8.74 (dt, J=9.3, 4.6 Hz, 1H), 8.41-8.52 (m, 2H), 7.68 (d, J=7.9 Hz, 1H), 7.02-7.17 (m, 1H), 5.29-5.61 (m, 1H), 4.18-4.84 (m, 4H), 4.16 (s, 3H), 3.87-4.09 (m, 1H), 1.62-1.91 (m, 2H), 1.41 (d, J=7.2 Hz, 2H), 0.82-0.97 (m, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (1.1 ml)
  3. stirringThe reaction was stirred at room temperature for 1 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resulting suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-1bd4d76598b04f15a3b6535d1860f566
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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