Acetic Acid → 9-Chloro-2-(2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydro-[1,2,4]triazolo[1,5-d][1,4]benzoxazepine

HRID 886245Notes

Reaction equation

HRID 886245 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]([N:11]=[C:12]([C:14]([NH2:16])=O)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.[C:19]1([CH3:25])C=CC=C[CH:20]=1.COC(OC)N(C)C.Cl.[CH:35]([NH:38][NH2:39])(C)C.C(O)(=O)C>>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]([N:11]=[C:12]([C:14]4[N:39]([CH:19]([CH3:25])[CH3:20])[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 582043089-Chloro-5,6-dihydrobenzo[f][1,2,4]triazolo[1,5-d][1,4]oxazepine-2-carboxamide

Product 1

HCID 582045269-Chloro-2-(2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydro-[1,2,4]triazolo[1,5-d][1,4]benzoxazepineYield 98%

Conditions

Temperature
102 °C

Procedure

To 9-Chloro-5,6-dihydrobenzo[f][1,2,4]triazolo[1,5-d][1,4]oxazepine-2-carboxamide (0.0053 g, 0.020 mmol) in toluene (0.160 mL, 1.50 mmol) was added 1,1-dimethoxy-N,N-dimethylmethanamine (0.0150 mL, 0.113 mmol), and the mixture was heated in a sealed flask to 102° C. for 2 hours while stirring. Next, the reaction mixture was cooled and concentrated to dryness, and isopropylhydrazine hydrochloride (0.00376 g, 0.0340 mmol) and acetic acid (0.0938 g, 1.56 mmol) were added and the reaction was sealed and heated to 102° C. overnight while stirring. Then, the reaction was concentrated to dryness and taken up in DMF, and purification by reverse phase HPLC gave 239 in 98% yield. 1H NMR (500 MHz, CDCl3) δ 8.56 (d, J=2.6 Hz, 1H), 8.02 (s, 1H), 7.35 (dd, J=8.8, 2.6 Hz, 1H), 7.06 (d, J=8.8 Hz, 1H), 5.84-5.66 (m, 1H), 4.84-4.70 (m, 2H), 4.62-4.47 (m, 2H), 1.61 (s, 6H). LRMS m/z Calcd. for C15H15ClN6O: 330.09959, Found: 331.1 [M+1]

Workup

  1. temperatureNext, the reaction mixture was cooled
  2. additionwere added
  3. customthe reaction was sealed
  4. temperatureheated to 102° C. overnight
  5. stirringwhile stirring
  6. concentrationThen, the reaction was concentrated to dryness
  7. custompurification by reverse phase HPLC

Sources & evidence

ORD record
ord-4efa007b72cb49608c80ebe010672ff1
Source dataset
uspto-grants-2012_08
Patent number
US08242104B2

Reaction notes

Loading…