Ethylenediamine → 2-(6-fluoro-1-piperidin-4-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246287Notes

Reaction equation

HRID 246287 reaction equation
[C:1]([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]([F:26])=[CH:23][CH:24]=4)[N:19]([CH:27]4[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]4)[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([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]([F:26])=[CH:23][CH:24]=4)[N:19]([CH:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712800342-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

Product 1

HCID 712800672-(6-fluoro-1-piperidin-4-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 89.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 10 ml round-bottomed flask, 2-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (46 mg, 0.069 mmol) was dissolved in dichloromethane (0.4 ml) and trifluoroacetic acid (0.22 ml, 2.86 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was suspended in dichloromethane (0.4 ml) and ethylenediamine (0.28 ml, 4.15 mmol) was added. The light yellow suspension was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The suspension was filtered and washed with hot water and ethyl acetate then dried under high vacuum to provide 27 mg (85%) of 2-(6-fluoro-1-piperidin-4-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow powder. MS: (M+H)+=436; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.08 (s, 1H), 8.47 (dd, J=8.9, 5.5 Hz, 1H), 8.39 (s, 1H), 7.96 (s, 1H), 7.77-7.85 (m, 1H), 7.10-7.22 (m, 1H), 4.70-4.88 (m, 1H), 3.13 (d, J=12.1 Hz, 2H), 2.67-2.81 (m, 2H), 2.01-2.20 (m, 2H), 1.88-2.01 (m, 2H), 1.52 (s, 9H).

Workup

  1. concentrationthen concentrated
  2. stirringThe light yellow suspension was stirred at room temperature for 1 h
  3. customthen quenched with water
  4. additiondiluted with ethyl acetate
  5. filtrationThe suspension was filtered
  6. washwashed with hot water and ethyl acetate
  7. customthen dried under high vacuum

Sources & evidence

ORD record
ord-6358ec004d0e4dddbb8b4b12be3425b2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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