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

HRID 245861

반응식

HRID 245861 반응식
C(OC(=O)[NH:7][CH:8]1[CH2:12][CH2:11][CH:10]([NH:13][C:14]([C:16]2[C:24]3[C:19](=[N:20][CH:21]=[C:22]([C:25]4[C:33]5[C:28](=[CH:29][C:30]([Cl:34])=[CH:31][CH:32]=5)[N:27]([CH3:35])[N:26]=4)[N:23]=3)[N:18](COCC[Si](C)(C)C)[CH:17]=2)=[O:15])[CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[NH2:7][CH:8]1[CH2:12][CH2:11][CH:10]([NH:13][C:14]([C:16]2[C:24]3[C:19](=[N:20][CH:21]=[C:22]([C:25]4[C:33]5[C:28](=[CH:29][C:30]([Cl:34])=[CH:31][CH:32]=5)[N:27]([CH3:35])[N:26]=4)[N:23]=3)[NH:18][CH:17]=2)=[O:15])[CH2:9]1

참가 물질

5

반응물 3

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71280283(3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-cyclopentyl)-carbamic acid tert-butyl ester

생성물 1

HCID 712882872-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclopentyl)-amide수율 78.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

In a round-bottomed flask, (3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-cyclopentyl)-carbamic acid tert-butyl ester (80 mg, 0.125 mmol) was dissolved in dichloromethane (0.7 ml) and trifluoroacetic acid (0.4 ml, 5.0 mmol) was added. The reaction mixture was stirred at room temperature for 3.5 h then concentrated. The residue was dissolved in dichloromethane (0.7 ml) and ethylenediamine (0.5 ml, 7.5 mmol) was added. The solution was stirred at room temperature for 2 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 40 mg (74%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclopentyl)-amide as an off-white powder. MS: (M+H)+=410; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 9.07 (s, 1H), 8.55 (d, J=8.7 Hz, 1H), 8.40 (s, 1H), 8.24 (d, J=7.6 Hz, 1H), 7.99 (s, 1H), 7.40 (d, J=9.1 Hz, 1H), 5.54 (br. s, 2H), 4.34-4.45 (m, 1H), 4.17 (s, 3H), 3.36-3.44 (m, 1H), 2.25-2.37 (m, 1H), 2.03-2.16 (m, 1H), 1.71-1.88 (m, 2H), 1.51-1.62 (m, 1H), 1.32-1.43 (m, 1H). The isolated product was determined to be a single diastereomer of unknown relative stereochemistry by NMR analysis.

후처리

  1. concentrationthen concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (0.7 ml)
  3. stirringThe solution was stirred at room temperature for 2 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

출처 및 근거

ORD 기록
ord-1b6d7b0f738045208712b4126fd68c21
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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