Dimethylformamide → (E)-8-chloro-2-methyl-5-(2-(pyrimidin-4-yl)prop-1-enyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400494Notes

Reaction equation

[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][N:16]=3)(O)[CH3:13])[C:6]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:5]=3[C:4]=2[CH:3]=1.CN(C=O)C.S(Cl)(Cl)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:11]=[C:12](/[C:15]3[CH:20]=[CH:19][N:18]=[CH:17][N:16]=3)\[CH3:13])[C:6]3[CH2:21][CH2:22][N:23]([CH3:25])[CH2:24][C:5]=3[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

1-(8-Chloro-2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-pyrimidin-4-yl-propan-2-ol (200 mg, 0.56 mmol) was dissolved in DCM (5 mL), and a drop of DMF was added. The solution was cooled to 0° C. and a solution of thionyl chloride (0.2 mL) in 1 mL DCM was added dropwise. The solution was stirred at RT for 30 min. and at RT for 2.5 h. Volatiles were evaporated under reduced pressure, the residue was basified with ice cold aqueous 1N NaOH (10 mL) and the product was extracted with EtOAc. The combined organic layer was washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by HPLC to obtain 14 mg of product as the TFA salt. 1H NMR (CD3OD, TFA salt) δ (ppm): 9.18 (s, 1H), 8.80 (d, 1H), 8.0 (s, 1H), 7.80 (d, 1H), 7.58 (s, 1H), 7.25 (m, 2H), 4.75 (m, 1H), 4.40 (m, 1H), 3.90 (m, 1H), 3.60 (m, 1H), 3.20 (m, 2H), 3.10 (s, 3H), 2.05 (s, 3H).

Workup

customVolatiles were evaporated under reduced pressure
extractionthe product was extracted with EtOAc
washThe combined organic layer was washed with water and brine
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified by HPLC

Sources & evidence

ORD record: ord-63e180cb2cf5439e8c8aea52ef3a7bfb
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906925B2

Reaction notes

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