Ethylenediamine → HCID 71288760, compound

HRID 245949Notes

Reaction equation

HRID 245949 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[C@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[N:13](COCC[Si](C)(C)C)[CH:12]=1)=[O:10])[CH3:7].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[O:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[C@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[NH:13][CH:12]=1)=[O:10])[CH3:7]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71288883HCID 71288883, compound

Product 1

HCID 71288760HCID 71288760, compoundYield 40.2%

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)—(S)-1-(tetrahydro-furan-2-yl)-ethyl]-amide (152 mg, 0.28 mmol) was dissolved in dichloromethane (1.4 ml) and trifluoroacetic acid (0.87 ml, 11.3 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (1.4 ml) and ethylenediamine (1.2 ml, 17.8 mmol) was added. The yellow solution 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 46 mg (40%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)—(S)-1-(tetrahydro-furan-2-yl)-ethyl]-amide as an off-white powder. MS: (M+Na)+=431; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.09 (br. s., 1H), 9.13 (s, 1H), 8.64 (dd, J=8.7, 5.3 Hz, 1H), 8.44 (s, 1H), 8.22 (d, J=9.4 Hz, 1H), 7.67 (d, J=8.3 Hz, 1H), 7.10 (t, J=8.1 Hz, 1H), 4.32 (br. s., 1H), 4.15 (s, 3H), 3.96 (d, J=3.0 Hz, 1H), 3.52-3.68 (m, 2H), 1.86-2.00 (m, 1H), 1.52-1.84 (m, 3H), 1.33 (d, J=6.8 Hz, 3H).

Workup

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (1.4 ml)
  3. stirringThe yellow solution 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-a8e900d5d85a4f88b675177e6d6a6bd0
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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