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 1498392Notes

Reaction equation

HRID 1498392 reaction equation
[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

Participants

6

Reactant 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

Product 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

Conditions

Temperature
85 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b437e7872d404e6f91a7e0ff8c9e5657
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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