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

HRID 246270Notes

Reaction equation

HRID 246270 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]([CH2:27][C:28]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[O:29])[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]([CH2:27][C:28]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[O:29])[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 71280344N-tert-Butyl-2-(6-fluoro-1-(2-morpholino-2-oxoethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712800232-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask, 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (81 mg, 0.13 mmol) was dissolved in dichloromethane (0.7 ml) and trifluoroacetic acid (0.41 ml, 5.32 mmol) was added. The yellow reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.7 ml) and ethylenediamine (0.54 ml, 8.00 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 and washed with hot water and ethyl acetate and dried under high vacuum to provide 38 mg (60%) of 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as an off-white powder. MS: (M+Na)+=502; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 12.81 (br. s., 1H), 9.04 (s, 1H), 8.49 (dd, J=8.8, 5.3 Hz, 1H), 8.40 (s, 1H), 7.95 (s, 1H), 7.62 (dd, J=10.0, 2.1 Hz, 1H), 7.16 (td, J=9.1, 2.3 Hz, 1H), 5.60 (s, 2H), 3.69-3.77 (m, 2H), 3.57-3.67 (m, 4H), 3.42-3.50 (m, 2H), 1.53 (s, 9H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.7 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-138fdaca220d4d6cb92b77492130cce8
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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