Ammonia → 9-Bromo-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-2-carboxamide

HRID 575454Notes

Reaction equation

HRID 575454 reaction equation
[Br:1][C:2]1[CH:20]=[CH:19][C:5]2[O:6][CH2:7][CH2:8][C:9]3[N:10]([N:11]=[C:12]([C:14](OCC)=[O:15])[CH:13]=3)[C:4]=2[CH:3]=1.[NH3:21]>>[Br:1][C:2]1[CH:20]=[CH:19][C:5]2[O:6][CH2:7][CH2:8][C:9]3[N:10]([N:11]=[C:12]([C:14]([NH2:21])=[O:15])[CH:13]=3)[C:4]=2[CH:3]=1

Participants

3

Reactant 2

HCID 222AmmoniaHCID 58204733Ethyl 9-bromo-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-2-carboxylate2×

Product 1

HCID 582043309-Bromo-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-2-carboxamideYield 89%

Conditions

Temperature
122.5 °C

Procedure

A suspension of ethyl 9-bromo-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-2-carboxylate (compound 61-4, page 196, WO 2011/036280) (0.3 g, 0.89 mmol) in 7 M ammonia solution (in methanol, 4 ml) was heated in a microwave apparatus to 120-125° C. for 2.5 hours. After cooling the mixture was left at room temperature for 18 hours before the solvent was removed in vacuo and the residue was then taken up in tetrahydrofuran and pre-absorbed onto a small amount of silica. Purification by FCC (silica, 20-100% ethyl acetate in heptane) gave 245 mg (89%) of the title compound. 1H NMR (250 MHz, DMSO-d6) 8 ppm 3.18 (2H, t, J=5.79 Hz), 4.46 (2H, t, J=5.79 Hz), 6.71 (1H, s), 7.18 (1H, dd, J=8.60, 0.69 Hz), 7.39 (1H, br, s.), 7.51 (1H, ddd, J=8.68, 2.44, 0.76 Hz), 7.84 (1H, br. s.), 8.19 (1H, dd, J=2.44, 0.76 Hz)); M+1=308/310.

Workup

  1. temperatureAfter cooling the mixture
  2. customwas removed in vacuo
  3. custompre-absorbed onto a small amount of silica
  4. customPurification by FCC (silica, 20-100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-436693777cfc49329d442a917dd98ae3
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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