Hydrazine hydrate (1:1) → tert-Butyl (1S,2R)-2-(5-oxo-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamate

HRID 2092731ノート

反応式

HRID 2092731 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([CH2:22][N:23]2[C:31](=[O:32])C3C(=CC=CC=3)C2=O)[C:19](C(OCC)=O)=[C:18]([NH:39][C:40]2[CH:41]=[C:42]([CH3:46])[CH:43]=[CH:44][CH:45]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.NN>CCO>[O:32]=[C:31]1[C:19]2[C:18]([NH:39][C:40]3[CH:41]=[C:42]([CH3:46])[CH:43]=[CH:44][CH:45]=3)=[N:17][C:16]([NH:15][C@@H:10]3[CH2:11][CH2:12][CH2:13][CH2:14][C@@H:9]3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[N:21][C:20]=2[CH2:22][NH:23]1

参加物

4

反応物 2

HCID 24654Hydrazine hydrate (1:1)HCID 58317681Ethyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylate

生成物 1

HCID 86654703tert-Butyl (1S,2R)-2-(5-oxo-4-(m-tolylamino)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-2-ylamino)cyclohexylcarbamate収率 44.2%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
65 °C

実験手順

A mixture of ethyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylate (109 mg, 0.174 mmol) and hydrazine hydrate (36.5 mg, 0.729 mmol) in EtOH (2 mL) was stirred at 65° C. for 12 h. After cooling, the mixture was concentrated under reduced pressure and the residue was treated with water and extracted with EtOAc. The combined organic layers were washed with aqueous NaHCO3, water, and brine, were filtered through SiO2, and the filtrate was concentrated under reduced pressure. The residue was recrystallized from EtOAc/hexanes and filtered to give the title compound (34.8 mg). The filtrate was concentrated and triturated with IPE to give a second batch (20.3 mg) of the title compound (total 65.1 mg, 83%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.24-1.79 (m, 17H), 2.32 (s, 3H), 3.84 (br s, 1H), 4.06 (br s, 1H), 4.14 (s, 2H), 6.55-6.70 (m, 1H), 6.87-7.04 (m, 2H), 7.20-7.24 (m, 1H), 7.40-7.48 (m, 1H), 7.68-7.80 (m, 1H), 8.01-8.06 (m, 1H), 8.56-8.59 (m, 1H). [M+H] calc'd for C24H33N6O3, 453. found, 453.

後処理

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated under reduced pressure
  3. additionthe residue was treated with water
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with aqueous NaHCO3, water, and brine
  6. filtrationwere filtered through SiO2
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was recrystallized from EtOAc/hexanes
  9. filtrationfiltered

出典と根拠

ORDレコード
ord-82f945ca7cd342f18400295ac27f1ea7
出典データセット
uspto-grants-2013_05
特許番号
US08440689B2

反応ノート

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