Ethylenediamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-cyanomethyl-cyclopentyl)-amide

HRID 245919Notes

Reaction equation

HRID 245919 reaction equation
[C:1]([CH2:3][C@@H:4]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=5)[N:23]([CH3:31])[N:22]=4)[N:19]=3)[N:14](COCC[Si](C)(C)C)[CH:13]=2)=[O:11])[CH2:5]1)#[N:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([CH2:3][C@@H:4]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[C:29]5[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=5)[N:23]([CH3:31])[N:22]=4)[N:19]=3)[NH:14][CH:13]=2)=[O:11])[CH2:5]1)#[N:2]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712855892-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-cyanomethyl-cyclopentyl)-amide

Product 1

HCID 712858612-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-cyanomethyl-cyclopentyl)-amideYield 78.1%

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 (cis-3-cyanomethyl-cyclopentyl)-amide (126 mg, 0.23 mmol) was dissolved in dichloromethane (1.2 ml) and trifluoroacetic acid (0.7 ml, 9.2 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (1.2 ml) and ethylenediamine (0.93 ml, 13.8 mmol) was added. The yellow solution was stirred at room temperature for 1.25 h then quenched with water and diluted with ethyl acetate. The resultant suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 75 mg (74%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-cyanomethyl-cyclopentyl)-amide as a light yellow powder. MS: (M+H)+=418; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.61 (br. s., 1H), 9.09 (s, 1H), 8.40-8.49 (m, 2H), 8.18 (d, J=7.2 Hz, 1H), 7.69 (dd, J=9.8, 2.3 Hz, 1H), 7.24 (td, J=9.2, 2.1 Hz, 1H), 4.29-4.45 (m, 1H), 4.15 (s, 3H), 2.66 (d, J=6.4 Hz, 2H), 2.34-2.43 (m, 1H), 2.23-2.34 (m, 1H), 2.11-2.23 (m, 1H), 1.85-2.00 (m, 1H), 1.46-1.74 (m, 2H), 1.28-1.41 (m, 1H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (1.2 ml)
  3. stirringThe yellow solution was stirred at room temperature for 1.25 h
  4. customthen quenched with water
  5. additiondiluted with ethyl acetate
  6. filtrationThe resultant suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-0a5022c91cc145f69dc85ad0b19758c2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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