Ethylenediamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyanomethyl-oxazol-2-yl)-ethyl]-amide

HRID 245944ノート

反応式

HRID 245944 の反応式
[C:1]([CH2:3][C:4]1[N:5]=[C:6]([C@H:9]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[N:16](COCC[Si](C)(C)C)[CH:15]=2)=[O:13])[CH3:10])[O:7][CH:8]=1)#[N:2].FC(F)(F)C(O)=O.C(N)CN>ClCCl>[C:1]([CH2:3][C:4]1[N:5]=[C:6]([C@H:9]([NH:11][C:12]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:23]4[C:31]5[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=5)[N:25]([CH3:33])[N:24]=4)[N:21]=3)[NH:16][CH:15]=2)=[O:13])[CH3:10])[O:7][CH:8]=1)#[N:2]

参加物

5

反応物 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712888822-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyanomethyl-oxazol-2-yl)-ethyl]-amide

生成物 1

HCID 712886992-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyanomethyl-oxazol-2-yl)-ethyl]-amide収率 65%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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)-1-(4-cyanomethyl-oxazol-2-yl)-ethyl]-amide (36 mg, 0.063 mmol) was dissolved in dichloromethane (0.4 ml) and trifluoroacetic acid (0.20 ml, 2.6 mmol) was added. The reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (0.4 ml) and ethylenediamine (0.26 ml, 3.8 mmol) was added. The yellow solution was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resultant suspension was filtered, washed with hot water and ethyl acetate and dried under high vacuum to provide 18 mg (65%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyanomethyl-oxazol-2-yl)-ethyl]-amide as an off-white powder. MS: (M+Na)+=467; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 12.93 (br. s., 1H), 9.12 (s, 1H), 8.66 (d, J=8.3 Hz, 1H), 8.50 (s, 1H), 8.46 (dd, J=8.9, 5.4 Hz, 1H), 8.06 (t, J=1.0 Hz, 1H), 7.69 (dd, J=9.7, 2.1 Hz, 1H), 7.12 (td, J=9.0, 2.3 Hz, 1H), 5.44-5.56 (m, 1H), 4.15 (s, 3H), 3.92 (d, J=1.3 Hz, 2H), 1.68 (d, J=7.0 Hz, 3H).

後処理

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.4 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 resultant suspension was filtered
  7. washwashed with hot water and ethyl acetate
  8. customdried under high vacuum

出典と根拠

ORDレコード
ord-3f6dc6d70b694cdaa825e2997d557156
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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