Water → 2-(6-fluoro-1-piperidin-4-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclopentyl)-amide

HRID 246316Notes

Reaction equation

HRID 246316 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=3)[C:16]([C:24]3[N:25]=[C:26]4[C:32]([C:33](=[O:48])[NH:34][CH:35]5[CH2:39][CH2:38][CH:37]([NH:40]C(OC(C)(C)C)=O)[CH2:36]5)=[CH:31][N:30](COCC[Si](C)(C)C)[C:27]4=[N:28][CH:29]=3)=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[NH2:40][CH:37]1[CH2:38][CH2:39][CH:35]([NH:34][C:33]([C:32]2[C:26]3[C:27](=[N:28][CH:29]=[C:24]([C:16]4[C:17]5[C:22](=[CH:21][C:20]([F:23])=[CH:19][CH:18]=5)[N:14]([CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)[N:15]=4)[N:25]=3)[NH:30][CH:31]=2)=[O:48])[CH2:36]1

Participants

7

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712805284-{3-[7-(3-tert-butoxycarbonylamino-cyclopentylcarbamoyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-6-fluoro-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 712883902-(6-fluoro-1-piperidin-4-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclopentyl)-amideYield 73%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a round-bottomed flask, 4-{3-[7-(3-tert-butoxycarbonylamino-cyclopentylcarbamoyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-6-fluoro-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (113 mg, 0.13 mmol) was dissolved in dichloromethane (0.7 ml) and trifluoroacetic acid (0.40 ml, 5.2 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.7 ml) and ethylenediamine (0.52 ml, 7.7 mmol) was added. The light yellow reaction was stirred at room temperature for 1 h then water and ethyl acetate were added. The resulting suspension was filtered and washed with hot water and ethyl acetate then dried under high vacuum to provide 43 mg (73%) of 2-(6-fluoro-1-piperidin-4-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclopentyl)-amide as an off-white powder.

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.7 ml)
  3. customThe light yellow reaction
  4. stirringwas stirred at room temperature for 1 h
  5. filtrationThe resulting suspension was filtered
  6. washwashed with hot water and ethyl acetate
  7. customthen dried under high vacuum

Sources & evidence

ORD record
ord-72b5f8d2d10d4cbeb18b5da5cf02d081
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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