Hydrochloric Acid → 8-Chloro-11-(piperazin-1-yl)-dibenzo[b,f][1,4]thiazepine

HRID 1437019Notes

Reaction equation

[Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[S:6][C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[C:9](=O)[NH:10][C:4]=2[CH:3]=1.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)Cl.[NH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.Cl>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[S:6][C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[C:9]([N:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)=[N:10][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of 8-chloro-10H-dibenzo[b,f][1,4]thiazepin-11-one (189JO13) (38 mg, 0.15 mmol) and N,N-dimethylaniline (46 μL, 0.36 mmol) in toluene was added POCl3 (27 μL, 0.29 mmol) and the resulting mixture was stirred for 2 h at 100° C., and then concentrated. Toluene (2 mL) and piperazine (62 mg, 0.73 mmol) were added, and the resulting mixture was stirred at 100° C. for 3 h, and then allowed to obtain room temperature. To the mixture was added aqueous HCl (1 mL, 2 M) and then the aqueous phase was extracted with EtOAc (2×2 mL). To the aqueous phase was added aqueous NaOH (3 mL, 2 M) and the resulting mixture was extracted with EtOAc (3×3 mL). The combined organic phases were concentrated and purified by HPLC to give 6.6 mg of the title compound (189JO16). MS (ESI) 330 (MH+). Purity for MH+ (UV/MS) 99/98.

Workup

concentrationconcentrated
stirringthe resulting mixture was stirred at 100° C. for 3 h
customto obtain room temperature
extractionthe aqueous phase was extracted with EtOAc (2×2 mL)
additionTo the aqueous phase was added aqueous NaOH (3 mL, 2 M)
extractionthe resulting mixture was extracted with EtOAc (3×3 mL)
concentrationThe combined organic phases were concentrated
custompurified by HPLC

Sources & evidence

ORD record: ord-5ae6b28ad035493f857cdca8759b4349
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07622461B2

Reaction notes

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