Phosphorus oxychloride → 10-chloro-1-methyl-3,8-dihydro-4H-[1,4]oxazepino[6,7-e]indole

HRID 2423198Notes

Reaction equation

[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][CH2:12][CH2:13][NH:14][C:15](=O)[CH3:16])[CH:9]=2)[N:4](S(C2C=CC=CC=2)(=O)=O)[CH:3]=1.O=P(Cl)(Cl)Cl>CCO.[OH-].[Na+].O.CC#N>[Cl:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]3[O:11][CH2:12][CH2:13][N:14]=[C:15]([CH3:16])[C:9]3=2)[NH:4][CH:3]=1

Participants

Conditions

Temperature: 75 °C

Procedure

N-(2-{[3-chloro-1-(phenylsulfonyl)-1H-indol-5-yl]oxy}ethyl)acetamide (Intermediate 39, 1.07 g, 2.73 mmol, ca 80% pure) in EtOH (25 ml) and 2 M NaOH (5 ml) were mixed and heated at 75° C. for 1 hour. The reaction mixture was cooled, diluted with water and extracted with DCM. The organic phase was dried (MgSO4) and evaporated to give the crude material (0.287 g) as a colorless oil. The crude material (0.250 g, 0979 mmol) was dissolved in MeCN (20 ml) and POCl3 was added. The reaction mixture was heated at 120° C. for 15 minutes in a microwave heater and evaporated. The crude material was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN) to give the title compound (99.7 mg) as a white solid. MS m/z 235 [M+H]+.

Workup

temperatureThe reaction mixture was cooled
extractionextracted with DCM
dry with materialThe organic phase was dried (MgSO4)
customevaporated
customto give the crude material (0.287 g) as a colorless oil
temperatureThe reaction mixture was heated at 120° C. for 15 minutes in a microwave heater
customevaporated
customThe crude material was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN)

Sources & evidence

ORD record: ord-24dfaefcb7384ff2925ba7c022b13fe6
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07960374B2

Reaction notes

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