Bis(2-chloroethyl)amine hydrochloride → 8-piperazin-1-yl-4H-benzo[1,4]oxazin-3-one

HRID 1750145Notes

Reaction equation

HRID 1750145 reaction equation
[NH2:1][C:2]1[C:7]2[O:8][CH2:9][C:10](=[O:12])[NH:11][C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl.Cl[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]Cl>ClC1C=CC=CC=1>[N:1]1([C:2]2[C:7]3[O:8][CH2:9][C:10](=[O:12])[NH:11][C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1

Participants

4

Reactant 2

HCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 117156098-piperazin-1-yl-4H-benzo[1,4]oxazin-3-oneYield 64.3%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Procedure

To a solution of intermediate 58 (164 mg, 1.0 mmol) in chlorobenzene (5 mL) was added bis(2-chloroethyl)amine hydrochloric acid (285 mg, 1.6 mmol) and the mixture was heated to reflux for 100 h. The reaction mixture was concentrated in vacuo and the residue was stirred in EtOAc for 2 h. The resulting brown solid was filtered and purified by silica gel chromatography to give 8-(piperazin-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (intermediate 59) (150 mg, 64%). HPLC: 99%, RT 1.344 min. MS (ESI) m/z 234.1[M+H]+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 100 h
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. filtrationThe resulting brown solid was filtered
  5. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-d956fb292ac74625a8961536ac21ccb0
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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