Acetic Acid → 9-chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine

HRID 1498392ノート

反応式

HRID 1498392 の反応式
[Cl:1][C:2]1[N:18]=[CH:17][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]([NH2:16])=O)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.COC(OC)N(C)C.[C:27]1([CH3:33])C=CC=C[CH:28]=1.Cl.[CH:35]([NH:38][NH2:39])(C)C.C(O)(=O)C>>[Cl:1][C:2]1[N:18]=[CH:17][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:39]([CH:27]([CH3:33])[CH3:28])[N:38]=[CH:35][N:16]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1

参加物

6

反応物 5

HCID 176Acetic AcidHCID 1140TolueneHCID 78373Dimethylformamide dimethyl acetalHCID 855731-Isopropylhydrazine hydrochlorideHCID 582042888-Chloro-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene-2-carboxylic acid amide

生成物 1

HCID 582045209-chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine

反応条件

温度
85 °C

実験手順

A mixture of [9-chloro-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine-2-carboxamide (0.520 g, 1.96 mmol) and 1,1-Dimethoxy-N,N-dimethylmethanamine (1.305 mL, 9.824 mmol) in Toluene (28.2 mL, 265 mmol) was heated under reflux for 1 hour. LCMS: no stm, major peak m/z 320.1. After cooling, the intermediate was concentrated. A mixture of the intermediate and isopropylhydrazine hydrochloride (0.4345 g, 3.929 mmol) in Acetic acid (18 mL, 320 mmol) was heated at 85° C. for 3 hours. The mixture was cooled and filtered from an insoluble impurity. The mother liquor was concentrated in vacuum. The residue was diluted with EtOAc then washed with water and brine. The organic layer was dried Na2SO4, filtered, and concentrated to give 317 (264). MS: (ESI+)=331.0. 1H NMR (400 MHz, DMSO) δ 9.29 (s, 1H), 7.97 (d, J=24.4 Hz, 1H), 7.94 (s, 1H), 7.31-7.19 (m, 1H), 5.85 (dq, J=13.0, 6.4 Hz, 1H), 4.66 (dd, J=5.2, 2.5 Hz, 2H), 4.63-4.54 (m, 2H), 1.48 (d, J=6.6 Hz, 6H).

後処理

  1. temperaturewas heated
  2. temperatureunder reflux for 1 hour
  3. temperatureAfter cooling
  4. concentrationthe intermediate was concentrated
  5. temperatureThe mixture was cooled
  6. filtrationfiltered from an insoluble impurity
  7. concentrationThe mother liquor was concentrated in vacuum
  8. additionThe residue was diluted with EtOAc
  9. washthen washed with water and brine
  10. filtrationfiltered
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-b437e7872d404e6f91a7e0ff8c9e5657
出典データセット
uspto-grants-2015_12
特許番号
US09198918B2

反応ノート

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