NL2035261A - Synthetic method for 3,4-dihydroisoquinolin-1-one compounds - Google Patents

Synthetic method for 3,4-dihydroisoquinolin-1-one compounds Download PDF

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Publication number
NL2035261A
NL2035261A NL2035261A NL2035261A NL2035261A NL 2035261 A NL2035261 A NL 2035261A NL 2035261 A NL2035261 A NL 2035261A NL 2035261 A NL2035261 A NL 2035261A NL 2035261 A NL2035261 A NL 2035261A
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formula
compound
synthesizing
dihydroisoquinoline
compounds according
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NL2035261A
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Dutch (nl)
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NL2035261B1 (en
Inventor
Wang Huan
Zhou Fan
Shuai Sujuan
Li Jie
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Hangzhou City Univ
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
    • C07D217/24—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention relates to a synthetic method for 3,4— dihydroisoguinolin—l—one compounds, including the following steps: under the protection of inert gas, dissolving a compound as shown in formula (I) in an aprotic solvent, and sequentially adding 1—2 5 mol/L tetrahydrofuran solvent of alkali and a compound as shown in formula (II) while stirring; and allowing reaction under heating conditions, and, then collecting a compound, as shown. in formula (III) from the reaction product; wherein aromatic groups in formula (I) and formula (II) are selected from any one of phenyl, IO substituted phenyl, naphthyl, pyridine, furan and thiophene. The present invention has the beneficial effects that the synthetic method for 3,4—dihydroisoguinolin—l—one compounds provided by the present invention is green, efficient, easy to operate, more widely applicable and more economical, and has very important 15 theoretical value and practical significance in the field. ° o m£î£5£5+æcîräiâRÆîïîfiîj m m M)‘;fi (+ Fig. l)

Description

P1807 /NL
SYNTHETIC METHOD FOR 3,4-DIHYDROISOQUINOLIN-1-ONE COMPOUNDS
TECHNICAL FIELD
The present invention relates to the field of organic synthe- sis, and particularly relates to a synthetic method for 3,4- dihydroisoguinolin-1l-one compounds.
BACKGROUND
3,4-dihydroisogquinolin-1-0ne compounds are the parent core structures widely existing in the natural alkaloids and the phar- maceutical industry. The representative alkaloids containing the 3,4-dihydroisoguinolin-1-0ne parent core include Corydaldine,
Thalifoline, N-methylcoryaldine, Minalrestat, Narciclasine and the like. Compounds containing such frame have a wide range of biolog- ical activities, such as anti human immunodeficiency virus, anti- bacterial, antidepressant, anticancer, antioxidant and antithrom- botic effects. Therefore, it has always been a research hotspot in the fields of medicinal chemistry and synthetic chemistry to de- velop an effective synthetic method for such important lactam ring core. ete AT 2
As RY : NH Ho Ar AQ Re : nN ST CL XX 1 OH it ì il i ì it . i a
LC mg $06 2 gr 9 TT
HN in
Corydalding Thalitoling N-methyl coryaidine Minslrastat Narsiclasine
At the early stage, the synthesis of 3,4-dihydroisoquinolin- l-one compounds mainly depended on the intramolecular cyclization of active amides or amide precursors, including carbamate, isocya- nate, azide amide and urea. However, the strong acidity conditions of these methods limit the range of substrates. In recent years, a large number of researches have been conducted on the preparation of such compounds, and the representative methods include: (1) palladium catalyzed carbonyl insertion method; (2) transition met- al catalyzed C-H bond activation method; (3) cyclohexylamine oxi- dation method; and (4) domino reaction without metal participa- tion, etc.
Intrrasoireudar syslizstion iN 9 1 Ce EEL gt a pg RE
RK is ¢ 5 Rg d
ED Carbonyl insenien 5 x : 1 H : ss pet ns + Zea piest, Er” nF
Riz 1 ie Satta
Ag OR Rr?
A= Lar OTR {23 Transition weil satalyaed CAE sotivation a 7 in eN Ay + gts ROR NN ™
Ha i it 4
R EJ TEN RE
Re
Kd, DMe, OBoq, or CE £3) Guidation of cycle wines 2 nN Re . i
PO LL VON va Med De $41 hos o o 5 oa > 5 rng RE al AR en 1 Ee A VIT ~
St uv [Jer oN DR | ar Safa on
NY we FR RE a a ro —~{_} ~My x 2
The above researches have provided several effective synthet- ic methods for the preparation of 3,4-dihydroisoquinolin-1-0ne.
Although substantial progress has been made and the methods have been applied in the pharmaceutical field, these methods still have some shortcomings that cannot be ignored, including use of transi- tion metals, pre-preparation of complex substrates, harsh reaction conditions and cumbersome post-treatment. Therefore, it has very important theoretical value and practical significance in this field to seek for a more widely applicable, economical, green and convenient synthetic method.
SUMMARY
The objective of the present invention is to overcome the de- fects existing in the prior art, and provide a synthetic method for 3,4-dihydroisoguinolin-1-0ne compounds, including the follow- ing steps:
S1. under the protection of inert gas, dissolving a compound as shown in formula (I) in an aprotic solvent, and sequentially adding 1-2 mol/L tetrahydrofuran solvent of alkali and a compound as shown in formula (II) while stirring; and 82. allowing reaction under heating conditions, and then col- lecting a compound as shown in formula (III) from the reaction product;
0 ©
RR ; Ry
OOS ED «CCX, ek A= ík,
FH
{1 {ny 8) wherein the aromatic groups in formula (I) and formula (IT) are selected from any one of phenyl, substituted phenyl, naphthyl, pyridine, furan and thiophene.
Preferably, in $82, a temperature of the reaction under the heating conditions is 60-100°%, and a reaction time is 12-16 h.
Preferably, in 31, the alkali is selected from sodium bis (trimethylsilyl)amide.
Preferably, a molar ratio of the compound in formula (I), the compound in formula (II) and the alkali is 1:1-2:2-3.
Preferably, in S1, the aprotic solvent is selected from any one of 1,4-dioxane, cyclopentyl methyl ether, toluene, tetrahydro- furan and dimethoxyethane.
The present invention has the advantages that the synthetic method for 3,4-dihydroisoquinolin-l-one compounds provided by the present invention is green, efficient, easy to operate, more wide- ly applicable and more economical, and has very important theoret- ical value and practical significance in the field.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a flow chart of a synthetic method for 3,4- dihydroisoquinolin-l-one compounds provided by the present inven- tion.
DETAILED DESCRIPTION OF THE EMBODIMENTS
The present invention will be further described below in com- bination with the embodiments. The description of the following embodiments is only for better understanding the present inven- tion. It should be noted that for those of ordinary skill in the art, some modifications may be made to the present invention with- out deviating from the principle of the present invention. These improvements and modifications should also fall into the protec- tion scope of the claims of the present invention.
A synthetic method for 3,4-dihydroisoquinclin-l-one compounds provided by the embodiments of the present invention is as fol-
lows:
Under the protection of inert gas, 0.2 mmol of compound as shown in formula (I) is dissolved in 2 mL of 1,4-dioxane or tolu- ene, and 0.24 mmol of compound as shown in formula (II) and 0.3 mL of tetrahydrofuran solvent containing 0.6 mmol of sodium bis(trimethylsilyl)amide (lithium bis (trimethylsilyl)amide may al- so be used) were sequentially added while stirring, reaction is allowed at 60-100°C for 12-16 h, then 3 drops of water are added for quenching, a small amount of silica gel powder and anhydrous sodium sulfate are used for filtration, evaporation under reduced pressure 1s performed after washing with ethyl acetate, and the mixture is separated using column chromatography (PE: EA=10:1-3:2) to obtain a product (III). i / A i xy 1,
A = Ca ze
U {1 (B wherein the aromatic groups in formula (I) and formula (II) are selected from any one of phenyl, substituted phenyl, naphthyl, pyridine, furan and thiophene.
The structure of a series of 3,4-dihydroisoguinolin-1-one de- rivatives synthesized by the present invention is as follows:
PQ Pg Pg Lg : Si RR - Ea * ZEN . DS ee “ay ha Bu Fp oF,
EN gs) (1-3) (id) ocr MM ot po OH a NH
IF AA # Ny AAAs
GIS) (6) (i167) {4i-8) pa a 0 Br OQ “> © { i | ! i
G> A : ANA SF Sy “Fr SN
J do lo = Sa oF rd
IB) {H-10} TH) {4-12} 5 » > in 1 SF 0 > Le? Q
YY IN f 5 NH i A oo Cy Cr. Ot.
SF 4 TC Ty {H-13) {i-14} UH-15} {1-18}
The following examples are for further explanation.
Example 1:
Preparation and characterization of compound III-1: 9
O / ap “No I NH cop Ur AAS 5 (1-1) {1-1} {= a 10 mL reaction tube was taken, and a stirrer was added. Un- der the protection of nitrogen gas, the compound (48.2 mg, 0.2 mmol) as shown in formula (I-1) was added, add 1,4 dioxane {2.0 mL} was added and dissolved by stirring, and 0.24 mmol of compound as shown in formula (II-1) and sodium bis (trimethylsilyl)amide (2.0 mol/L, 0.3 mL, 0.6 mmol) were sequentially added; after re- acting at 100°C for 12 h, 3 drops of water were added for quench- ing, a small amount of silica gel powder and anhydrous sodium sul- fate were used for filtration, evaporation under reduced pressure was performed after washing with ethyl acetate, and the mixture was eluted using column chromatography (PE: EA=10:1) to obtain a compound III-1; the compound III-1 was white solid, and a yield was 88%; 'H NMR (500 MHz,CDCls): & 7.41 - 7.35 (m, 4H), 7.34 — 7.31 (m, 1H), 6.96 (s, 1H), 6.82 (s, 1H), 6.55 (s, 1H), 4.72(dd, J= 11.2, 4.0 Hz, 1H), 3.13 (dd, J=15.3, 11.2 Hz, 1H), 3.00 (dd, J= 15.3, 4.2 Hz, 1H}, 2.68 (s, 3H), 2.31 (s, 3H).
Example 2
Preparation and characterization of compound III-2:
Oo
Te) 7 i , NH
NTR + AJ me =~ DD ‘Buy (1-1) (11-2) (1-2)
The preparation conditions were the same as those in example 1. The compound III-2 was white solid, and a yield was 86%; ‘H NMR (500 MHz, CDCl): & 7.43 — 7.40 (m, 2H), 7.35 - 7.32 (m, 2H), 6.97 (s, 1H), 6.84 (s,1H), 6.10 (s, 1H), 4.71 (dd, J=11.8, 4.0 Hz, 1H), 3.16 (dd, J=15.3, 11.8 Hz, 1H), 2.97 (dd, J=15.3, 3.8 Hz, 1H), 2.69 (s, 3H), 2.32 (s, 3H), 1.33 (s, SH).
Example 3
Preparation and characterization of compound III-3:
Q
Oo | , we So "NH
SNS C
" ze ’ Ph (1) (1-3) (11-3)
The preparation conditions were the same as those in example 1. The compound III-3 was white solid, and a yield was 91%; ‘H NMR (500 MHz, CDCl): & 7.62-7.58 (m, 4H), 7.48-7.44 (m, 4H), 7.39 - 7.35 (Im, 1H), 6.98 (s, 1H), 6.85 (s, 1H), 6.24 (s, 1H), 4.78 (dd,
J = 11.4, 4.1 Hz, 1H), 3.19 (dd, J = 15.3, 11.3 Hz, 1H), 3.05 (dd, J = 15.3, 4.1 Hz, 1H), 2.71 (s, 3H), 2.33(s, 3H).
Example 4
Preparation and characterization of compound III-4:
OG
= ;
AA 4 NY Soi TM ® rt Fac TN “CF {1-1} {1-4} 4)
The preparation conditions were the same as those in example 1. The compound III-4 was white solid, and a yield was 81%; :H NMR (500 MHz, CDCl;3): & 7.62 (d, J = 8.0Hz, 2H), 7.51 (d, J = 8.0 Hz, 5 2H), 6.96 (s, 1H), 6.81 (s, 1H), 6.76 (s, 1H), 4.82 (t, J = 7.5
Hz, 1H), 3.13 - 3.09 (m, 2H), 2.64 {(s, 3H), 2.30 (s, 3H).
Example 5
Preparation and characterization of compound III-5:
Nx + Fo “Oo NH
X . p= 9 moe F | ]
I
F
{i-1) (1-5) {1ii-8)
The preparation conditions were the same as these in example 1. The compound III-5 was light yellow solid, and a yield was 75%; 'H NMR (500 MHz, CDCls): & 7.39 - 7.34 (m, 2H), 7.08 — 7.03 (m, 2H), 6.96 (s, 1H), 6.82 (s, 1H), 6.24 (s, 1H), 4.72 (dd, J = 11.2, 4.2Hz, 1H), 3.11 (dd, J = 15.3, 11.1 Hz, 1H), 3.00 (dd, J = 15.3, 4.2 Hz, 1H), 2.67 {s, 3H), 2.31 (s, 3H).
Example 6
Preparation and characterization of compound III-6:
Q AN
“Oo | NH Ci
ON + —
NF
(-1) (11-6) {11-6}
The preparation conditions were the same as those in example 1. The compound III-6 was white solid, and a yield was 84%; ‘H NMR (500 MHz, CDCl:): & 7.46 (dd, J = 7.3, 2.1 Hz,1H}, 7.38 (dd, J = 7.5, 1.7 Hz, 1H), 7.28 - 7.22 (m, 2H), 6.96 (s, 1H), 6.82 (s, 1H), 6.12 {(s, 1H}, 5.25 - 5.22 {m, 1H), 3.23 (dd, J = 15.4, 4.8 Hz,
1H), 3.06 (dd, J = 15.4, 9.2 Hz, 1H), 2.70 {(s, 3H), 2.30 (s, 3H).
Example 7
Preparation and characterization of compound III-7:
O o I
No i NH = ES , Sed N | N rE 1-1) (1-7) (1-7)
The preparation conditions were the same as those in example 1. The compound III-7 was white solid, and a yield was 70%; ‘H NMR (500 MHz, CDCl:): & 8.60 (d, J = 2.2 Hz, 1H), 8.55 (dd, J = 4.8, 1.6 Hz, 1H), 7.74 - 7.72 (m, 1H), 7.31 - 7.28 (m, 1H), 6.95 (s, 1H), 6.80 (s, 1H), 6.58 (s, 1H), 4.80 - 4.77 {(m, 1H), 3.15 - 3.08 {m, 2H), 2.64 (s, 3H), 2.29 (s, 3H).
Example 6
Preparation and characterization of compound III-8:
Oo 0 + 3 do | | Sor” “NH y — { 3 YW 2 s
Sn
Ww 1) {1-8} (11-8)
The preparation conditions were the same as those in example 1. The compound III-8 was white solid, and a yield was 86%; *‘H NMR {500 MHz, CDCl:): & 7.23 (dd, J = 5.1, 1.2 Hz, 1H), 7.04 - 7.03 {m, 1H), 6.98 - 6.95 (m, 2H), 6.85 (s, 1H), 6.31 (s, 1H), 5.01 - 4.98 (rm, 1H), 3.21 (dd, J = 15.3, 9.7 Hz, 1H), 3.16 (dd, JT = 15.3, 4.7 Hz, 1H), 2.67 (s, 3H), 2.31 (s, 3H).
Example 9
Preparation and characterization of compound III-9: 0
QO
“po i NH re 2, TC {1-2) {1-1} {11-8}
The preparation conditions were the same as those in example 1. The compound III-9 was white solid, and a yield was 87%; ‘H NMR (500 MHz, CDCl:): & 7.42 — 7.37 (m, 4H), 7.35 - 7.32 (m, 1H), 7.29 {t, 3 = 7.5 Hz, 1H}, 7.15 (d, J = 7.6 Hz, 1H), 7.02 (d, J = 7.4
Hz, 1H), 6.38 (s, 1H), 4.75 (dd, J = 11.5, 4.1 Hz, 1H), 3.19 (dd,
J = 15.3, 11.4 Hz, 1H), 3.05 (dd, 0 = 15.4, 4.1 Hz, 1H), 2.72 (s, 3H).
Example 10
Preparation and characterization of compound III-10: cl 0
Cl OQO rT No i NH
Ny fl | ‚ í C (1-3) {H-1) (11-10) ;
The preparation conditions were the same as those in example 1 except for the selected aprotic solvent and the reaction temper- ature. DME was used as the solvent, and the reaction was performed at 80°C; the compound III-10 was white solid, and a yield was 87%; 'H NMR (500 MHz, CDCls): & 7.41 — 7.30 (m, 7H), 7.09 (d, J = 7.4
Hz, 1H), 6.31 (s, 1H), 4.78 — 4.74 (m, 1H), 3.21 (dd, J = 15.4, 11.1 Hz, 1H), 3.09 (dd, J = 15.4, 4.0 Hz, 1H).
Example 11
Preparation and characterization of compound III-11:
Br OQ
Br Oo oo «Rp NH
VON + | — mw
OL 5 © (4) {1-1} (1-11)
The preparation conditions were the same as those in example 1 except for the reaction temperature, and the reaction was per- formed at 60°C; the compound III-11 was white solid, and a yield was 83%; 'HNMR (500 MHz, CDCl:): & 7.62 (d, J = 7.9 Hz, 1H}, 7.42 — 7.33 (m, SH), 7.22 (t, J = 7.7 Hz, 1H), 7.15 (d, J = 7.4 Hz,
1H), 6.21 (s, 1H), 4.78 - 4.74 (m, 1H), 3.24 (dd, J = 15.4, 11.3
Hz, 1H), 3.09 (dd, J = 15.3, 3.8 Hz,1lH).
Example 12
Preparation and characterization of compound III-12: ~. .
Q 0 >> i gy + | J Rl {IS +
CD mg MEF Ne
SF
Le (8) en (12)
The preparation conditions were the same as those in example 1. The compound III-12 was white solid, and a yield was 89%; *‘H NMR {500 MHz; CDCl3)}: & 7.40 - 7.35 (m, 5H), 7.34 - 7.31 (m, 1H}, 6.91 (d, J = 8.4 Hz, 1H), 6.76 (d, J = 7.4 Hz, 1H), 6.01 (s, 1H), 4.74 - 4.71 (m, 1H), 3.94 (s, 3H), 3.17 (dd, J = 15.3, 11.2 Hz, 1H), 3.04 (dd, J = 15.3, 3.8 Hz, 1H).
Example 13
Preparation and characterization of compound III-13:
Ph ©
Ph ©
Xv Np i x NH + [0 ee (1-6) (1-1) (11-13)
The preparation conditions were the same as those in example 1. The compound III-13 was white solid, and a yield was 98%; *‘H NMR (500 MHz, CDCl:): & 7.46 — 7.41 (m, 5H), 7.40 — 7.33 (m, GH), 7.24 (d, J = 7.5 Hz, 1H), 7.20 (d, J = 7.4 Hz, 1H), 6.06 (s, 1H), 4.90 - 4.87 {(m, 1H), 3.28 (dd, J = 15.5, 10.8Hz, 1H), 3.18 (dd, J = 15.6, 4.1 Hz, 1H).
Example 14
Preparation and characterization of compound III-14:
Sz / 0
O 0 i me + a. NH
NTN
= CC {-7) (H-1} {in-14)
The preparation conditions were the same as those in example 1. The compound III-14 was white solid, and a yield was 60%; ‘H NMR (500 MHz, CDCl:): & 7.44 - 7.34 {(m, 8H), 7.19 (d, J = 7.3 Hz, 1H), 7.08 - 7.05 (m, 2H), 6.11 (s, 1H), 4.87 - 4.84 (m, 1H), 3.26 (dd,
J = 15.6, 10.8 Hz, 1H), 3.16 (dd, J = 15.6, 4.2 Hz, 1H).
Example 15
Preparation and characterization of compound III-15:
N
N >)
SY HE
“oo ey Ng i © 4 de i { e= ih = NH
Sy NTA i 6 yi SEEN
NC A
{8} {1-1} (1-13)
The preparation conditions were the same as those in example 1. The compound III-15 was white solid, and a yield was 92%; ‘H NMR {500MHz, CDCl:): & 8.57 —- 8.56 {m, ZH), 7.46 (t, J = 7.6 Hz, 1H), 7.42 - 7.33 {(m, SH), 7.26 - 7.24 (m, 3H), 7.14 (d, J = 7.5 Hz, 1H), 6.16 (s, 1H), 4.88 - 4.85 {(m, 1H), 3.27 (dd, J = 15.7, 10.7
Hz, 1H), 3.18 (dd, J = 15.6, 4.4 Hz, 1H).
Example 16
Preparation and characterization of compound III-16:
NT
NT Ry id 7 0
NP re Ry i :
GQ + ij | — 5
Jl Ls NH
TOONT ° Le jj ee
Lo Jef a a i pr {9} {H-1} 1-18}
The preparation conditions were the same as those in example 1. The compound III-16 was white solid, and a yield was 85%; ‘H NMR
(500MHz, CDCl,): & 8.55 — 8.53 (m, 2H), 7.68 — 7.66 (m, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.42 — 7.33 (m, 5H), 7.28 (dd, J = 7.8, 4.9
Hz, 1H), 7.25 (d, J = 7.9 Hz, 1H), 7.19 (d, J = 7.6 Hz, 1H), 6.20 (s, IH), 4.88 — 4.85 (m, 1H), 3.27 (dd, J = 15.6, 10.7 Hz, 1H), 3.19 (dd, J = 15.6, 4.3 Hz, 1H).

Claims (7)

CONCLUSIESCONCLUSIONS 1. Werkwijze voor het synthetiseren van 3,4-dihydroisochinoline-1- on-verbindingen, omvattende de volgende stappen:1. Method for synthesizing 3,4-dihydroisoquinoline-1-one compounds, comprising the following steps: Sl. onder bescherming van inert gas, oplossen van een verbinding zoals weergegeven in formule (I) in een aprotisch oplosmiddel, en achtereenvolgens toevoegen van 1-2 mol/L tetrahydrofuranoplosmid- del van alkali en een verbinding zoals weergegeven in formule (II) onder roeren; enSl. under protection of inert gas, dissolving a compound represented by formula (I) in an aprotic solvent, and successively adding 1-2 mol/L tetrahydrofuran solvent of alkali and a compound represented by formula (II) under stirring; and S2. laten reageren onder verhittingsomstandigheden, en vervolgens een verbinding verzamelen zoals weergegeven in formule (III) uit het reactieproduct; o ? Al a SN aS rel N RY + Fy ss “Ri Cost An LA =~ Da Le U i {uy waarbij aromatische groepen in formule (I) en formule (II) zijn gekozen uit één van fenyl, gesubstitueerd fenyl, naftyl, pyridine, furan en thiofeen.S2. react under heating conditions, and then collect a compound as shown in formula (III) from the reaction product; oh ? Al a SN aS rel N RY + Fy ss “Ri Cost An LA =~ Da Le U i {uy where aromatic groups in formula (I) and formula (II) are selected from one of phenyl, substituted phenyl, naphthyl, pyridine, furan and thiophene. 2. Werkwijze voor het synthetiseren van 3,4-dihydroisochinoline-1- on verbindingen volgens conclusie 1, waarbij in S2 de temperatuur van de reactie onder de verhittingsomstandigheden 60-100°C is en de reactietijd 12-16 uur is.A method for synthesizing 3,4-dihydroisoquinoline-1-one compounds according to claim 1, wherein in S2 the temperature of the reaction under the heating conditions is 60-100°C and the reaction time is 12-16 hours. 3. Werkwijze voor het synthetiseren van 3,4-dihydroisochinoline-1- on verbindingen volgens conclusie 2, waarbij in S1 de alkali wordt gekozen uit natriumbis(trimethylsilyl)amide.A method for synthesizing 3,4-dihydroisoquinoline-1-one compounds according to claim 2, wherein in S1 the alkali is selected from sodium bis(trimethylsilyl)amide. 4. Werkwijze voor het synthetiseren van 3,4-dihydroisochinoline-1- on verbindingen volgens conclusie 3, waarbij in Sl een molaire verhouding van de verbinding met formule (I) tot de verbinding met formule (II) tot de base is 1: 1-2: 2-3.A method for synthesizing 3,4-dihydroisoquinoline-1-one compounds according to claim 3, wherein in S1 a molar ratio of the compound of formula (I) to the compound of formula (II) to the base is 1:1 -2:2-3. 5. Werkwijze voor het synthetiseren van 3,4-dihydroisochincline-1- on verbindingen volgens conclusie 4, waarbij in 31 het aprotische oplosmiddel wordt gekozen uit elk van 1,4-dioxaan, cyclopentylme- thylether, tolueen, tetrahydrofuran en dimethoxyethaan.A method for synthesizing 3,4-dihydroisoquincline-1-one compounds according to claim 4, wherein in 31 the aprotic solvent is selected from any of 1,4-dioxane, cyclopentyl methyl ether, toluene, tetrahydrofuran and dimethoxyethane. 6. Werkwijze voor het synthetiseren van 3,4-dihydroisochinoline-1- on verbindingen volgens conclusie 5, waarbij in S1 het inerte gas stikstofgas is.A method for synthesizing 3,4-dihydroisoquinoline-1-one compounds according to claim 5, wherein in S1 the inert gas is nitrogen gas. 7. Werkwijze voor het synthetiseren van 3,4-dihydroisochinoline-1- on verbindingen volgens conclusie 6, waarbij S2 de volgende stap- pen omvat: S201. reactie onder verhitting mogelijk maken; S202. water toevoegen om te blussen; S203. het filteren van het reactieproduct met silicagelpoeder en watervrij natrium; en S204. het uitvoeren van verdamping onder verlaagde druk na het wassen van het reactieproduct met ethylacetaat, en het scheiden van het mengsel met behulp van kolomchromatografie (PE: EA=10:1- 3:2) om een verbinding te verkrijgen zoals getoond in formule (III).A method for synthesizing 3,4-dihydroisoquinoline-1-one compounds according to claim 6, wherein S2 comprises the following steps: S201. enable reaction under heating; S202. add water to extinguish; S203. filtering the reaction product with silica gel powder and anhydrous sodium; and S204. carrying out evaporation under reduced pressure after washing the reaction product with ethyl acetate, and separating the mixture by column chromatography (PE: EA=10:1-3:2) to obtain a compound as shown in formula (III ).
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