Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.C([Mg]Cl)(C)C.[CH2:16]([Sn:20]([CH2:26][CH2:27][CH2:28][CH3:29])([CH2:22][CH2:23][CH2:24][CH3:25])Cl)[CH2:17][CH2:18][CH3:19]>C1COCC1.CCCCCC>[CH2:26]([Sn:20]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:22][CH2:23][CH2:24][CH3:25])[C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1)[CH2:27][CH2:28][CH3:29]
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: Ic1cnc2ccccn12
Agent: CC(C)[Mg]Cl
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1cnc2ccccn12
Temperature: 20 °C
Reaction time: 0.5 h

Procedure:
In a 100 mL three-necked flask, 3-iodoimidazo[1,2-a]pyridine (0.9 g, 3.69 mmol) was dissolved in 50 ml THF at −5° C. using an acetone/ice bath. Isopropylmagnesium chloride (1.3 M, 2.84 ml, 3.69 mmol) was added via a syringe and a light white suspension formed. After 0.5 h, tributylchlorostannane (1.15 g, 0.95 μl, 3.69 mmol) was added. This was stirred at 20° C. for 1.5 h. The reaction mixture was diluted with hexane (100 ml), quenched with a saturated solution of ammonium chloride and the organics were washed with 50% brine/water. The organic layer was dried over sodium sulfate, filtered and concentrated to give 3-tributylstannanyl-imidazo[1,2-a]pyridine as an oil. 1H NMR (300 MHz, CDCl3) δ 8.03 (d, 1H) 7.61 (d, 1H) 7.59 (s, 1H) 7.17 (m, 1H) 6.72 (m, 1H) 0.9-1.55 (m, 27).
Reaction SMILES: [CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][C:9](=[O:12])[CH:8]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:7]2)=[O:5])[CH2:3][CH2:2]1.[BH4-].[Na+]>C(O)C>[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][C@@H:9]([OH:12])[C@H:8]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:7]2)=[O:5])[CH2:2][CH2:3]1
Reactant: O=C1CCN(C(=O)C2CC2)CC1c1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: O=C(C1CC1)N1CC[C@@H](O)[C@H](c2ccccc2)C1

Procedure:
A solution of 4.77 g 1-cyclopropylcarbonyl-3-phenyl-4-piperidone in 50 ml of absolute ethanol is cooled to 4° C. and treated dropwise under nitrogen with a solution of 0.74 g of sodium borohydride in 50 ml of absolute ethanol over a 10 minute period, keeping the pot temperature below 10° C. After the addition is complete, the bath is removed. The mixture is cooled while diluting with 100 ml of saturated sodium chloride solution and, after stirring for a few minutes the ethanol is removed in vacuo and the aqueous residue is extracted with dichloromethane (1×150 ml, 2×100 ml). The combined dichloromethane extracts are washed with 150 ml of saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil. The oil is chromatographed on 190 g of silica gel using ether as solvent followed by 5%, 10% and finally 50% acetone/ether mixture. The cis-isomer is eluted first followed by the trans-isomer as a colorless solid. Recrystallization from 5 ml of ethyl acetate affords product as a colorless crystalline solid, mp, 125°-127.5° C.
Reaction SMILES: [NH:1]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:2]([C:4]([NH:6][C@H:7]([C:9]([NH:11][C@H:12]([C:14]([OH:16])=O)[CH3:13])=[O:10])[CH3:8])=[O:5])[CH3:3].[NH2:24][CH2:25][CH2:26][CH2:27][OH:28].C1COCC1>CN(C=O)C>[NH:1]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:2]([C:4]([NH:6][C@H:7]([C:9]([NH:11][C@H:12]([C:14]([NH:24][CH2:25][CH2:26][CH2:27][OH:28])=[O:16])[CH3:13])=[O:10])[CH3:8])=[O:5])[CH3:3]
Reactant: C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)OC(C)(C)C)C(=O)O
Reactant: NCCCO
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NCCCO

Procedure:
The desired compound was synthesized by the procedure of Example 4 using Boc-Ala-Ala-Ala-OH and H2N—(CH2)3—OH except that the solvent was a mixture of THF and DMF (8 h). In a typical reaction of 4.59 mmol scale, the desired product was obtained in good yields, (1.401 gm, 79%) as a solid (m.p.—201° C.) after purification by silica gel flash column chromatography (MeOH:EtOAc—1:25). TLC (MeOH:DCM—1: 3; Rf—0.53).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[CH:3]=[CH:2]1.Cl.[CH3:11][NH:12][CH3:13].C=O>C(O)CCC>[CH3:11][N:12]([CH3:13])[C:3]1[C:4]2[C:9](=[N:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1
Reactant: CNC
Reactant: c1cnc2[nH]ccc2c1
Agent: C=O
Agent: Cl
Solvent: CCCCO
Product: CN(C)c1c[nH]c2ncccc12
Yield: 88.2 %

Procedure:
To 40 ml of n-butyl alcohol was added 1.18 g of 7-azaindole, 0.88 g of dimethylamine hydrochloride and 0.33 g of paraformaldehyde, and the mixture refluxed for 30 minutes. The clear solution was then evaporated to dryness in vacuo, and 10 ml of 10% aqueous hydrochloric acid was added to the residue. The water layer was extracted with ether, and then made strongly basic with potassium carbonate. The resulting precipitate was filtered off, washed with ether and dried, yielding 1.42 g (81.1%) of 3-dimethylamino-7-azaindole, m.p. 144°-152° C.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:13]=[CH:12][C:7]2[O:8][CH:9]=[CH:10][O:11][C:6]=2[CH:5]=1)=[O:3].[Li].C[Si]([NH-])(C)C.Cl[Si](C)(C)C.[C:25]1([CH2:31][S:32][CH:33]([C:37](O)=[O:38])[C:34](O)=[O:35])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[K+].[Br-]>>[O:8]1[C:7]2[CH:12]=[CH:13][C:4]([C:2]3[O:3][C:34](=[O:35])[C:33]([S:32][CH2:31][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[C:37]([OH:38])[CH:1]=3)=[CH:5][C:6]=2[O:11][CH2:10][CH2:9]1
Reactant: CC(=O)c1ccc2c(c1)OC=CO2
Reactant: O=C(O)C(SCc1ccccc1)C(=O)O
Agent: C[Si](C)(C)Cl
Agent: C[Si](C)(C)[NH-]
Agent: [Br-]
Product: O=c1oc(-c2ccc3c(c2)OCCO3)cc(O)c1SCc1ccccc1

Procedure:
The title compound was prepared by Method A using 1,4-benzodioxin-6-yl methyl ketone (2.5 g, 14.25 mmol), lithium bis(trimethylsilylamide (2.35 g, 14.25 mmol), chlorotrimethylsilane (2.47 g, 14.25 mmol) and diethyl ester of [(phenylmethyl)thio]propanedioic acid (1.00 g, 3.55 mmol). m.p. 192-193° C.; 1H NMR (400 MHz, DMSO-d6) δ3.99 (s, 2 H), 4.17 (m, 4 H), 6.8 (s, 1 H), 7.0 (d, 1 H), 7.2 (m, 1 H), 2.28 (m, 7 H); IR (KBr) 3435, 2924, 1649, 1624, 1508, 1288, 1066, 698 cm-1 ; MS (CI): m/e 369 (M+H,), 277 (12), 233 (12), 163 (9), 107 (10), 91 (76); Analysis calc'd for C20H16O5S1 : C, 65.21; H, 4.38; found: C, 64.80; H, 4.17.
Reaction SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Si]([O:26][CH2:27][CH2:28][C:29]1[CH:30]=[C:31]([CH2:34][N:35]2[CH2:56][CH2:55][C:38]3([O:43][CH2:42][CH2:41][N:40]([C:44]([C:46]4[N:47]=[C:48]([C:51]([CH3:54])([CH3:53])[CH3:52])[S:49][CH:50]=4)=[O:45])[CH2:39]3)[CH2:37][CH2:36]2)[S:32][CH:33]=1)(C(C)(C)C)(C)C>C1COCC1>[C:51]([C:48]1[S:49][CH:50]=[C:46]([C:44]([N:40]2[CH2:39][C:38]3([CH2:55][CH2:56][N:35]([CH2:34][C:31]4[S:32][CH:33]=[C:29]([CH2:28][CH2:27][OH:26])[CH:30]=4)[CH2:36][CH2:37]3)[O:43][CH2:42][CH2:41]2)=[O:45])[N:47]=1)([CH3:54])([CH3:52])[CH3:53]
Reactant: CC(C)(C)c1nc(C(=O)N2CCOC3(CCN(Cc4cc(CCO[Si](C)(C)C(C)(C)C)cs4)CC3)C2)cs1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CC(C)(C)c1nc(C(=O)N2CCOC3(CCN(Cc4cc(CCO)cs4)CC3)C2)cs1

Procedure:
TBAF (1.5 mL of a 1M solution in THF) was added to stirred solution of (9-((4-(2-(tert-butyldimethylsilyloxy)ethyl)thiophen-2-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-tert-butylthiazol-4-yl)methanone (example 43, step c) (0.300 g) in THF (3 mL). After 1 h the reaction was evaporated to a gum. Purification by silica gel chromatography eluting with ethyl acetate:triethylamine, 20:1 gave the subtitled compound as a gum. Yield 0.22 g.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:14]([C:15]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[C:16]4[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]4)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:4][CH:3]=1.[CH:28]1[C:40]2[NH:39][C:38]3[C:33](=[CH:34][C:35]([C:41]4[CH:59]=[CH:58][C:44]([N:45]([C:52]5[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=5)[C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=5)=[CH:43][CH:42]=4)=[CH:36][CH:37]=3)[C:32]=2[CH:31]=[C:30]([C:60]2[CH:78]=[CH:77][C:63]([N:64]([C:71]3[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=3)[C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)=[CH:62][CH:61]=2)[CH:29]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CCCCCC.C1(C)C=CC=CC=1>[C:22]1([C:15]2[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:8]([C:5]3[CH:4]=[CH:3][C:2]([N:39]4[C:40]5[CH:28]=[CH:29][C:30]([C:60]6[CH:61]=[CH:62][C:63]([N:64]([C:65]7[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=7)[C:71]7[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=7)=[CH:77][CH:78]=6)=[CH:31][C:32]=5[C:33]5[C:38]4=[CH:37][CH:36]=[C:35]([C:41]4[CH:42]=[CH:43][C:44]([N:45]([C:52]6[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=6)[C:46]6[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=6)=[CH:58][CH:59]=4)[CH:34]=5)=[CH:7][CH:6]=3)=[C:9]3[C:14]=2[CH:13]=[CH:12][CH:11]=[CH:10]3)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: c1ccc(N(c2ccccc2)c2ccc(-c3ccc4[nH]c5ccc(-c6ccc(N(c7ccccc7)c7ccccc7)cc6)cc5c4c3)cc2)cc1
Reactant: Brc1ccc(-c2c3ccccc3c(-c3ccccc3)c3ccccc23)cc1
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: CC(C)(C)[O-]
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: c1ccc(-c2c3ccccc3c(-c3ccc(-n4c5ccc(-c6ccc(N(c7ccccc7)c7ccccc7)cc6)cc5c5cc(-c6ccc(N(c7ccccc7)c7ccccc7)cc6)ccc54)cc3)c3ccccc23)cc1
Yield: 41.9 %

Procedure:
0.70 g (1.7 mmol) of 9-(4-bromophenyl)-10-phenylanthracene, 1.1 g (1.7 mmol) of 4,4′-(9H-carbazol-3,6-diyl)bis(N,N-diphenylaniline) (TP2C), and 0.49 g (9.0 mmol) of sodium tert-butoxide were put into a 100 mL three-neck flask. The air in the flask was replaced with nitrogen. Then, to the mixture were added 30 mL of toluene and 0.20 mL of tri(tert-butyl)phosphine (a 10 wt % hexane solution). This mixture was stirred to be degassed while the pressure was reduced. After the degassing, 46 mg (0.080 mmol) of bis(dibenzylideneacetone)palladium(0) was added to the mixture. This mixture was stirred at 110° C. for 3 hours under a stream of nitrogen. After the stirring, the mixture was subjected to suction filtration through celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855), alumina, and Florisil (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 540-00135). The obtained filtrate was condensed to give a light yellow solid. This solid was recrystallized with toluene/hexane to give 0.70 g of a light yellow powder, which was the object of the synthesis, at a yield of 42%. A synthesis scheme of Step 2 is shown in (e-2) given below.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:4]=1[CH:13]([NH2:17])[CH2:14][CH2:15][CH3:16].[F:20][C:21]([F:31])([F:30])[C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=1>>[F:1][C:2]([F:18])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:10])([F:11])[F:12])=[CH:5][C:4]=1[CH:13](/[N:17]=[CH:26]/[C:25]1[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:30])[F:31])=[CH:29][CH:28]=1)[CH2:14][CH2:15][CH3:16]
Reactant: O=Cc1ccc(C(F)(F)F)cc1
Reactant: CCCC(N)c1cc(C(F)(F)F)ccc1C(F)(F)F
Product: CCCC(/N=C/c1ccc(C(F)(F)F)cc1)c1cc(C(F)(F)F)ccc1C(F)(F)F
Reaction time: 0.5 h

Procedure:
A mixture of 1-[2,5-bis(trifluoromethyl)phenyl]butan-1-amine (2.95 g, 10.3 mmol) and 4-trifluoromethyl benzaldehyde (1.8 g, 10.3 mmol) was swirled together for 30 minutes. M/Z (ES+) 442 (ME).
Reaction SMILES: C([O:3][C:4](=[O:25])[CH:5]([CH2:13][S:14]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1)(=[O:16])=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)C.Cl>>[CH3:24][O:23][C:20]1[CH:19]=[CH:18][C:17]([S:14]([CH2:13][CH:5]([CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4]([OH:25])=[O:3])(=[O:16])=[O:15])=[CH:22][CH:21]=1
Reactant: CCOC(=O)C(Cc1ccccc1)CS(=O)(=O)c1ccc(OC)cc1
Agent: Cl
Product: COc1ccc(S(=O)(=O)CC(Cc2ccccc2)C(=O)O)cc1
Temperature: 115 °C
Yield: 89.7 %

Procedure:
A mixture of 0.56 g (1.5 mmol) of 2-[(4-methoxybenzenesulfonyl)methyl]-3-phenyl-propanoic acid ethyl ester and 8 ml of 6N HCl is heated at 115° C. for 17 hours. The mixture is transferred to 100 ml of ice-water and extracted with two portions of ethyl acetate. The organic phase is extracted with three 50 mL portions of aqueous 5% sodium bicarbonate. The bicarbonate solution is poured over ice and acidified with concentrated HCl. The acidified aqueous mixture is extracted with three 50 mL portions of ethyl acetate and the combined organic extracts are concentrated in vacuo to yield 0.45 g of the title compound as a white solid.
Reaction SMILES: [OH-].[K+].[CH3:3][O:4][C:5](=[O:31])[CH:6]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22](=[O:30])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:29])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.[Br:32][CH2:33][CH2:34]Br>C(O)C>[CH3:3][O:4][C:5](=[O:31])[CH:6]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22](=[O:30])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:29])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH2:34][CH2:33][Br:32])=[CH:12][CH:13]=1
Reactant: COC(=O)C(Cc1ccc(O)cc1)Nc1ccccc1C(=O)c1ccccc1C
Reactant: BrCCBr
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: COC(=O)C(Cc1ccc(OCCBr)cc1)Nc1ccccc1C(=O)c1ccccc1C
Yield: 56.7 %

Procedure:
To a solution of potassium hydroxide (0.17 g, 2.95 mmol) in ethanol (20 ml) is added 2-[(2-(2-methylbenzoyl)phenyl)amino]-3-(4-hydroxyphenyl)-propionic acid methyl ester (1.15 g, 2.95 mmol) and 1,2-dibromoethane (5.54 g, 29.50 mmol). Then the mixture is heated to reflux for 8 hours. After cooled, the reaction mixture is filtered to remove the solid formed, and then the filtrate is evaporated under a vacuum. The crude product is purified by silica gel chromatography using hexane/EtOAc (4:1) as eluent to give the title compound (0.83 g, 57%).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[N:3]=1.[C:17]1([CH:23]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[N:24]2[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][OH:32])[CH2:26][CH2:25]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[H-].[Na+]>O1CCCC1>[C:33]1([CH:23]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:24]2[CH2:25][CH2:26][N:27]([CH2:30][CH2:31][O:32][C:2]3[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]4[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=4)[N:3]=3)[CH2:28][CH2:29]2)[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1
Reactant: COc1ccc(-c2nc(C)cc(Cl)n2)cc1
Reactant: OCCN1CCN(C(c2ccccc2)c2ccccc2)CC1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(-c2nc(C)cc(OCCN3CCN(C(c4ccccc4)c4ccccc4)CC3)n2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 47.4 %

Procedure:
0.6 g of 4-chloro-2-(4-methoxyphenyl)-6-methylpyrimidine and 0.76 g of 1-diphenylmethyl-4-(2-hydroxyethyl)piperazine were dissolved in 20 ml of dried tetrahydrofuran. After addition of 0.1 g of 60% sodium hydride, the mixture was stirred for 20 hours at room temperature. The reaction mixture was poured into ice-water and was extracted with ethyl acetate. After the extract was washed with water and was dried with anhydrous magnesium sulfate, then was evaporated in vacuo. The resulting residue was purified with column chromatography with silica gel (Wako gel C-200, elution with chloroform and then chloroform:ethyl acetate=8:1). The desired fraction was crystallized by evaporating the solvent under reduced pressure. The crystals were recrystallized with the solvent mixed with chloroform and ether, resulting to obtain 0.6 g of crystals. Melting point is 132° to 133° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:36])[CH2:9][CH2:10][CH:11]2[CH:14]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[N:13]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][CH2:32][CH2:33]F)=[CH:25][CH:24]=3)[C:12]2=[O:35])=[CH:4][CH:3]=1.[CH3:37][NH:38][CH2:39][CH2:40][S:41]([OH:44])(=[O:43])=[O:42].C(=O)([O-])[O-].[K+].[K+]>CO.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([OH:36])[CH2:9][CH2:10][CH:11]2[C:12](=[O:35])[N:13]([C:23]3[CH:24]=[CH:25][C:26]([O:29][CH2:30][CH2:31][CH2:32][CH2:33][N:38]([CH3:37])[CH2:39][CH2:40][S:41]([OH:44])(=[O:43])=[O:42])=[CH:27][CH:28]=3)[CH:14]2[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)=[CH:6][CH:7]=1
Reactant: CNCCS(=O)(=O)O
Reactant: COc1ccc(C2C(CCC(O)c3ccc(F)cc3)C(=O)N2c2ccc(OCCCCF)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: COc1ccc(C2C(CCC(O)c3ccc(F)cc3)C(=O)N2c2ccc(OCCCCN(C)CCS(=O)(=O)O)cc2)cc1
Temperature: 50 °C
Reaction time: 24 h
Yield: 31 %

Procedure:
130 mg of 3-[3-(4-fluorophenyl)-3-hydroxypropyl]-1-[4-(4-fluorobutoxy)phenyl]-4-(4-methoxyphenyl)azetidin-2-one (7) were dissolved in 6 ml of absolute methanol. 120 mg of N-methyltaurine in 2 ml of water and 60 mg of potassium carbonate were then added. The mixture was stirred at 50° C. for 24 h. The reaction mixture was concentrated using a rotary evaporator and the residue was purified by preparative chromatography. Freeze-drying gave the product (50 mg) as an oil.
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:13])=[CH:4][C:5]([Br:12])=[C:6]([CH2:8][C:9](=O)[CH3:10])[CH:7]=1.[NH2:14][C:15]1[C:20]([CH:21]=O)=[CH:19][N:18]=[C:17]([S:23][CH3:24])[N:16]=1.[O-]CC.[Na+]>CCO>[Br:12][C:5]1[C:6]([C:8]2[C:9]([CH3:10])=[N:14][C:15]3[N:16]=[C:17]([S:23][CH3:24])[N:18]=[CH:19][C:20]=3[CH:21]=2)=[CH:7][C:2]([NH2:1])=[C:3]([F:13])[CH:4]=1
Reactant: CSc1ncc(C=O)c(N)n1
Reactant: CC(=O)Cc1cc(N)c(F)cc1Br
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CSc1ncc2cc(-c3cc(N)c(F)cc3Br)c(C)nc2n1
Temperature: 25 °C
Reaction time: 12 h
Yield: 16.2 %

Procedure:
Treat a solution of 1-(5-amino-2-bromo-4-fluorophenyl)propan-2-one (5 g, 27.62 mmol) and 4-amino-2-methylsulfanyl-pyrimidine-5-carbaldehyde (4.67 g, 27.62 mmol) in EtOH (30 mL) with sodium ethoxide (3.76 g, 55.25 mmol) and stir at RT for 12 h. Concentrate the mixture to dryness, treat with water, extract with EtOAc (3×), wash the combined organics with brine, dry with Na2SO4, concentrate and purify by silica gel chromatography (EtOAc/Pet Ether, 1:4) to afford the title compound (1.7 g, 16% yield). MS (m/z): 379.1/381.1 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([C:8]2[O:9][C:10]3[CH:17]=[CH:16][C:15]([O:18]CC=C)=[CH:14][C:11]=3[C:12]=2[CH3:13])=[O:7])=[CH:4][CH:3]=1.Cl[C:25]1[CH:30]=CC=C[C:26]=1Cl>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:8]2[O:9][C:10]3[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([CH2:30][CH:25]=[CH2:26])[C:11]=3[C:12]=2[CH3:13])=[O:7])=[CH:22][CH:23]=1
Reactant: Clc1ccccc1Cl
Reactant: C=CCOc1ccc2oc(C(=O)c3ccc(F)cc3)c(C)c2c1
Product: C=CCc1c(O)ccc2oc(C(=O)c3ccc(F)cc3)c(C)c12
Yield: 76 %

Procedure:
A solution of 2-(p-fluorobenzoyl)-3-methyl-5-allyloxybenzofuran (2.77 gm; 9.2 mmoles) in ortho-dichlorobenzene (15 mL) was refluxed under nitrogen for a period of 4 hours. On cooling, the reaction product crystallized. Some hexane was added and the crystals were filtered, washed with hexane and air-dried to yield 2.1 gm (76%) of 2-(p-fluorobenzoyl)-3-methyl-4-allyl-5-hydroxybenzofuran, mp. 164°-166° C.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11](=[O:19])[NH:12][CH2:13][C:14]([O:16]CC)=[O:15].[OH-].[K+].Cl>O>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11](=[O:19])[NH:12][CH2:13][C:14]([OH:16])=[O:15]
Reactant: CCOC(=O)CNC(=O)Nc1nc2ccccc2s1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: O=C(O)CNC(=O)Nc1nc2ccccc2s1
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 82.3 %

Procedure:
The compound was synthesized by hydrolysis method. 100 mg of ethyl 2-(3-benzo[d]thiazole-2-ylureido)acetate and 60 mg of KOH were added to 10 ml of water, and subjected to reflux under 100° C. for 2 hours. The obtained reaction mixture were stirred at room temperature for 30 minutes, and cooled in ice-bath. Then, 1 ml of strong hydrochloric acid was added thereto, to acidify the obtained reaction mixture. 74 mg of 2-(3-benzo[d]thiazole-2-ylureido)acetic acid was produced in white solid phase.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:7][CH2:6][C:5]1=[O:16].[H-].[Na+].Cl[C:20]1[C:29]2[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=2)[N:23]=[CH:22][CH:21]=1>CN(C=O)C>[CH3:31][O:30][C:26]1[CH:25]=[C:24]2[C:29]([C:20]([O:1][CH2:2][CH2:3][N:4]3[CH2:9][CH:8]([C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)[CH2:7][CH2:6][C:5]3=[O:16])=[CH:21][CH:22]=[N:23]2)=[CH:28][CH:27]=1
Reactant: O=C1CCC(c2ccccc2)CN1CCO
Reactant: COc1ccc2c(Cl)ccnc2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc2c(OCCN3CC(c4ccccc4)CCC3=O)ccnc2c1
Temperature: 23 °C
Reaction time: 0.17 h

Procedure:
To a stirring solution of 1-(2-hydroxyethyl)-5-phenylpiperidin-2-one (100 mg, 456 μmol) in DMF (1.5 mL) under nitrogen was added NaH (60% dispersion in mineral oil; 16 mg, 684 μmol). The suspension was stirred for 10 min at 23° C., then 4-chloro-7-methoxyquinoline (132 mg, 684 μmol) was added. After 2 h at 23° C. the reaction mixture was partitioned between CH2Cl2 (15 mL) and 5% NaHCO3 (10 mL). The aqueous was extracted with CH2Cl2 (5 mL) twice. The organics were dried over MgSO4, concentrated to a solid from toluene under reduced pressure. Purification on silica (12 g) eluting with 10>40% of 5% MeOH/CH2Cl2 afforded a white solid from acetonitrile. 1H NMR (400 MHz, Chloroform-d) δ ppm 1.95-2.09 (m, 2 H) 2.40-2.64 (m, 2 H) 2.97-3.09 (m, 1H) 3.63 (t, J=11.35 Hz, 1 H) 3.68-3.76 (m, 1 H) 3.88 (t, J=4.99 Hz, 2 H) 3.94 (s, 3 H) 4.36-4.47 (m, 2 H) 6.65 (d, J=5.28 Hz, 1 H) 7.08 (dd, J=9.19, 2.54 Hz, 1 H) 7.16 (d, J=6.85 Hz, 2 H) 7.22-7.34 (m, 3 H) 7.38 (d, J=2.35 Hz, 1 H) 7.96 (d, J=9.00 Hz, 1 H) 8.66 (d, J=5.28 Hz, 1 H).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7](Br)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])([CH3:4])([CH3:3])[CH3:2].[Mg].Br[C:16]1[S:20][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH:18][CH:17]=1>C1COCC1.[Cl-].[Zn+2].[Cl-]>[C:1]([C:5]1[CH:6]=[C:7]([C:16]2[S:20][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH:18][CH:17]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)c1ccc(Br)s1
Reactant: COc1ccc(Br)cc1C(C)(C)C
Agent: [Cl-]
Agent: [Mg]
Agent: [Zn+2]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(-c2ccc(OC)c(C(C)(C)C)c2)s1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 2 g (8.2 mmol) of 3-tert-butyl-4-methoxybromobenzene is added dropwise to a suspension of 300 mg (12 mmol) of magnesium in 10 ml of THF. Once the addition is complete, the mixture is refluxed for one hour. At room temperature, 1.35 g (9.9 mmol) of anhydrous zinc chloride are added and the mixture is stirred for one hour. 1.2 g (5.5 mmol) of methyl 5-bromo-2-thiophenecarboxylate and 60 mg (0.12 mmol) of the NiCl2/DPPE complex are then added successively and the mixture is left stirring at room temperature for 12 hours. The reaction medium is poured into ice-water and extracted with ethyl ether and the organic phase is separated out after settling has taken place, dried over magnesium sulphate and evaporated. The residue obtained is chromatographed on a column of silica eluted with a mixture of hexane and dichloromethane (50/50% by volume). After evaporation of the solvents, 1.56 g (93%) of the expected methyl ester are collected, with a melting point of 94-5° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9](=[O:11])[CH3:10])=[CH:5][CH:4]=1.[BrH:12].BrBr>C(O)(=O)C>[BrH:12].[Br:12][CH2:10][C:9]([C:6]1[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:11]
Reactant: COc1ccc(C(C)=O)cn1
Agent: Br
Agent: BrBr
Solvent: CC(=O)O
Product: COc1ccc(C(=O)CBr)cn1

Procedure:
230 mg (1.52 mmol) of 1-(6-methoxypyrid-3-yl)ethanone, 413 μl (7.61 mmol) of hydrobromic acid, 87 μl (1.67 mmol) of bromine and 5 mL of glacial acetic acid were used in the reaction. After precipitation with ethyl ether and filtration, 430 mg of 2-bromo-1-(6-methoxypyrid-3-yl)ethanone hydrobromide are obtained, the characteristics of which are as follows: