1,2-Dimethoxyethane → 8-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

HRID 886194ノート

反応式

HRID 886194 の反応式
[Br:1][C:2]1[CH: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.[CH3:19]OC(OC)N(C)C.COCCOC.Cl.[CH:34]([NH:37][NH2:38])([CH3:36])[CH3:35]>C(O)(=O)C>[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:37]([CH:34]([CH3:36])[CH3:35])[N:38]=[CH:19][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 4

HCID 80711,2-DimethoxyethaneHCID 78373Dimethylformamide dimethyl acetalHCID 855731-Isopropylhydrazine hydrochlorideHCID 582046299-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

生成物 1

HCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene収率 39%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
65 °C

実験手順

9-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide (4.93 g, 16.0 mmol) was taken up in 1,1-dimethoxy-N,N-dimethylmethanamine (25 mL, 0.18 mol) and 1,2-dimethoxyethane (66.5 mL, 0.640 mol). The heterogeneous mixture was stirred very vigorously and heated at 65° C. for 1 h. LC/MS showed complete consumption of starting material at the end of this period. The reaction mixture was concentrated in vacuo and carried on to the subsequent reaction with no further purification steps applied. The crude product from the previous reaction (5.8 g, 16.0 mmol) was suspended in glacial acetic acid (53.2 mL) and isopropylhydrazine hydrochloride (4.36 g, 39.4 mmol) was added. The mixture was heated at 100° C. for 2 h. The reaction vessel was cooled to room temp and the solvent was removed in vacuo. The resultant residue was dry loaded onto silica gel and purified by ISCO chromatography (120 g column, 100% EtOAc). In total, 2.3 g (39% yield) of 194 was isolated over the two steps. LC/MS (ESI+): m/z 376 (M+H, with halide isotope). 1H NMR (400 MHz, DMSO) δ 8.34 (d, J=8.6, 1H), 7.95 (s, 1H), 7.91 (s, 1H), 7.36 (dd, J=8.7, 2.0, 1H), 7.30 (d, J=2.0, 1H), 5.85 (dt, J=13.3, 6.6, 1H), 4.55 (d, J=15.5, 4H), 1.48 (d, J=6.6, 6H)

後処理

  1. customconsumption of starting material at the end of this period
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customcarried on to the subsequent reaction with no further purification steps
  4. temperatureThe mixture was heated at 100° C. for 2 h
  5. temperatureThe reaction vessel was cooled to room temp
  6. customthe solvent was removed in vacuo
  7. dry with materialThe resultant residue was dry
  8. custompurified by ISCO chromatography (120 g column, 100% EtOAc)

出典と根拠

ORDレコード
ord-63c3a8b75a3f4aa694f5e4f6d71da29d
出典データセット
uspto-grants-2012_08
特許番号
US08242104B2

反応ノート

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