Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]([CH:9]2[CH:14]3[CH2:15][CH:11]4[CH:12]([CH2:13]3)[CH:10]24)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:16][N:17]1[CH2:21][CH2:20][CH2:19][CH:18]1[CH:22](Cl)[CH3:23]>CS(C)=O>[CH3:16][N:17]1[CH2:21][CH2:20][CH2:19][CH:18]1[CH2:22][CH2:23][O:8][C:7](=[C:9]1[CH:14]2[CH2:15][CH:11]3[CH:12]([CH2:13]2)[CH:10]13)[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(c1ccccc1)C1C2CC3C(C2)C31
Reactant: CC(Cl)C1CCCN1C
Solvent: CS(C)=O
Product: CN1CCCC1CCOC(=C1C2CC3C(C2)C13)c1ccccc1
Temperature: 25 °C

Procedure:
5.28 g. (0.11 mol) of a 50% sodium hydride/mineral oil dispersion were purified as in Example 6, followed by the dropwise addition while stirring under nitrogen of 80 ml. of dimethyl sulphoxide. The reaction mixture was then heated for 30 minutes at 70°-80° C. until the evolution of hydrogen stopped, after which it was cooled to room temperature and a solution of 19.83 g. (0.1 mol) of tricyclo-(2.2.1.02.6)-hept-3-yl phenyl ketone in 25 ml. of dimethyl sulphoxide added dropwise to it. After stirring for another hour at 35°-40° C., 16.25 g. (0.11 mol) of N-methyl pyrrolidyl-2-ethyl chloride in 15 ml. of dimethyl sulphoxide were added and the mixture stirred for another 2.5 hours at 35° to 40° C. The reaction mixture was then poured into 300 ml. of water, the oil precipitated was extracted with ether and the ether phase dried with anhydrous sodium sulphate. Filtration and concentration of the solvent by evaporation in vacuo left an oily residue which was converted into the hydrochloride in chloroform with 2N hydrochloric acid.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH2:32][CH2:31][C:30]([CH3:34])([CH3:33])[CH2:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([C:18]([C@H:20]1[CH2:25][CH2:24][C@H:23]([CH3:26])[CH2:22][CH2:21]1)=[O:19])[CH:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]1)=[O:4].[BH4-].[Na+].Cl>CO>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH2:32][CH2:31][C:30]([CH3:33])([CH3:34])[CH2:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([C@H:11]1[CH2:16][CH2:15][C@H:14]([OH:17])[CH2:13][CH2:12]1)[C:18]([C@H:20]1[CH2:25][CH2:24][C@H:23]([CH3:26])[CH2:22][CH2:21]1)=[O:19])=[O:4].[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH2:32][CH2:31][C:30]([CH3:33])([CH3:34])[CH2:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([C@H:11]1[CH2:16][CH2:15][C@@H:14]([OH:17])[CH2:13][CH2:12]1)[C:18]([C@H:20]1[CH2:25][CH2:24][C@H:23]([CH3:26])[CH2:22][CH2:21]1)=[O:19])=[O:4]
Reactant: COC(=O)c1sc(C2=CCC(C)(C)CC2)cc1N(C(=O)[C@H]1CC[C@H](C)CC1)C1CCC(=O)CC1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)c1sc(C2=CCC(C)(C)CC2)cc1N(C(=O)[C@H]1CC[C@H](C)CC1)[C@H]1CC[C@@H](O)CC1
Product: COC(=O)c1sc(C2=CCC(C)(C)CC2)cc1N(C(=O)[C@H]1CC[C@H](C)CC1)[C@H]1CC[C@H](O)CC1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 5-(4,4-dimethyl-cyclohex-1-enyl)-3-[(trans-4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester (13.3 g, previous reaction) in 195 mL of MeOH at 0° C. was added NaBH4 (450 mg, 11.9 mmol) portion wise. The reaction mixture was stirred for 1 hour at 0° C. After completion of the reaction, HCl (1N) was slowly added. The mixture was evaporated to dryness and the residue partitioned in EtOAc and water. The water phase was extracted (3×) and the combined organic phase was washed with brine, dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel column chromatography using (30:70) EtOAc:hexane as eluent to obtain 5-(4,4-dimethyl-cyclohex-1-enyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (5155 mg) as a solid and 5-(4,4-dimethyl-cyclohex-1-enyl)-3-[(cis-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (789 mg) as a solid. The overall yield for steps III, IV and V was 51%.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C@@:20]3([CH2:24][O:23][C:22]([NH2:25])=[N:21]3)[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:26]4[CH2:27][CH2:28][O:29][CH2:30][CH:31]=4)[CH:18]=3)[O:13][C:10]2=[CH:11][CH:12]=1)(=O)=O.[Cl:34][C:35]1[CH:36]=[CH:37][C:38]([F:44])=[C:39](B(O)O)[CH:40]=1.CN(C=O)C.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([F:44])=[C:37]([C:7]2[CH:8]=[C:9]3[C@@:20]4([CH2:24][O:23][C:22]([NH2:25])=[N:21]4)[C:19]4[C:14](=[N:15][CH:16]=[C:17]([C:26]5[CH2:27][CH2:28][O:29][CH2:30][CH:31]=5)[CH:18]=4)[O:13][C:10]3=[CH:11][CH:12]=2)[CH:36]=1
Reactant: OB(O)c1cc(Cl)ccc1F
Reactant: NC1=N[C@@]2(CO1)c1cc(OS(=O)(=O)C(F)(F)F)ccc1Oc1ncc(C3=CCOCC3)cc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: NC1=N[C@@]2(CO1)c1cc(-c3cc(Cl)ccc3F)ccc1Oc1ncc(C3=CCOCC3)cc12
Temperature: 70 °C
Reaction time: 1 h

Procedure:
A vial was charged with (S)-2′-amino-3-(3,6-dihydro-2H-pyran-4-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazole]-7-yl trifluoromethanesulfonate (0.050 g, 0.103 mmol), 5-chloro-2-fluorophenylboronic acid (0.054 g, 0.310 mmol), and Pd(PPh3)4 (5.97 mg, 5.17 μmol). The vial was purged with Ar (g). Then, DMF (0.517 mL) and potassium carbonate (0.259 mL, 0.517 mmol) (as a 2.0 M aq. solution) were added in sequence. The vial was sealed and stirred at 70° C. for one hour. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep 40 g, gradient elution 0-7% MeOH in DCM) to afford (S)-7-(5-chloro-2-fluorophenyl)-3-(3,6-dihydro-2H-pyran-4-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a white solid. Found MS: MH+=464.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[C:15](Br)[CH:16]=[CH:17][CH:18]=2)[C:13]([O:21][C@@H:22]2[O:48][C@H:47]([CH2:49][O:50][C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[C@@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:31]([O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[C@H:23]2[O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[N:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:57]([O:64][C:65]1[CH:70]=[CH:69][CH:68]=[C:67]([CH:71]=[CH2:72])[CH:66]=1)[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1.C(N(CC)CC)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[C:15](/[CH:72]=[CH:71]/[C:67]3[CH:68]=[CH:69][CH:70]=[C:65]([O:64][CH2:57][C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=4)[CH:66]=3)[CH:16]=[CH:17][CH:18]=2)[C:13]([O:21][C@@H:22]2[O:48][C@H:47]([CH2:49][O:50][C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[C@@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:31]([O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[C@H:23]2[O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[N:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)C(=O)OC[C@H]1O[C@@H](Oc2nn(CCOCc3ccccc3)c3cccc(Br)c23)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Reactant: C=Cc1cccc(OCc2ccccc2)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CC#N
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CC(C)(C)C(=O)OC[C@H]1O[C@@H](Oc2nn(CCOCc3ccccc3)c3cccc(/C=C/c4cccc(OCc5ccccc5)c4)c23)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 93.9 %

Procedure:
A mixture of 1-(2-benzyloxyethyl)-4-bromo-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indazole (0.85 g), 1-benzyloxy-3-vinylbenzene (0.32 g), triethylamine (2 mL), palladium (II) acetate (11 mg) and tris(2-methylphenyl)-phosphine (30 mg) in acetonitrile (8 mL) was heated for reflux under an argon atmosphere overnight. The reaction mixture was cooled to room temperature and diluted with diethyl ether, and the resulting mixture was stirred for 30 minutes. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−3/1) to give 1-(2-benzyloxyethyl)-4-[(E)-2-(3-benzyloxyphenyl)vinyl]-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indazole (0.92 g). This material was dissolved in ethyl acetate (10 mL). To the solution was added 10% palladium-carbon powder (0.3 g), and the mixture was stirred at room temperature under a hydrogen atmosphere overnight. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=2/1−1/1) to give the title compound (0.68 g).
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH:11]([CH3:13])[CH:10]([C:14]2[NH:19][C:18](=[O:20])[C:17]3=[CH:21][N:22]=[CH:23][N:16]3[N:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[I:29]I>C1COCC1>[CH2:1]([N:8]1[CH2:12][CH:11]([CH3:13])[CH:10]([C:14]2[NH:19][C:18](=[O:20])[C:17]3=[CH:21][N:22]=[C:23]([I:29])[N:16]3[N:15]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: II
Reactant: CC1CN(Cc2ccccc2)CC1c1nn2cncc2c(=O)[nH]1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC1CN(Cc2ccccc2)CC1c1nn2c(I)ncc2c(=O)[nH]1
Temperature: -45 °C
Reaction time: 0.5 h
Yield: 66 %

Procedure:
To a solution of compound 5 (1.0 g, 3.24 mmol) in dry THF (70 mL) was added n-BuLi (2.5 M, 2 mL) dropwise at −78° C. over 30 minutes. The reaction was stirred at −45° C. for 30 minutes. Then a solution of iodine in THF (20 mL) was dropwise added at −78° C. over 10 minutes. The resulting mixture was stirred at 0° C. for 2 hours. The reaction was quenched with saturated aqueous Na2S2O3 solution (10 mL). Then the reaction mixture was diluted with EtOAc (200 mL), and washed with brine (50 mL×2). The separated organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluted by PE/EtOAc=10:1 to 2:1) to afford compound 6 (930 mg, 66% yield) as a white solid. LC-MS: m/z 435.99 [M+1]+. 1H NMR (400 MHz, CDCl3): δ 7.89 (s, 1H), 7.37˜7.26 (m, 5H), 3.82 (d, J=12.4 Hz, 1H), 3.59 (d, J=12.4 Hz, 1H), 3.42˜3.38 (m, 1H), 2.98 (d, J=8.4 Hz, 1H), 2.82˜2.81 (m, 1H), 2.55˜2.51 (m, 1H), 2.45˜2.42 (m, 1H), 1.96˜1.92 (m, 1H), 1.22 (d, J=7.2 Hz, 3H).
Reaction SMILES: [O:1]=[C:2]1[NH:6][CH2:5][C:4]2([CH2:10][C@@H:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[N:8]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:7]2)[O:3]1.[Cl:25][C:26]1[CH:27]=[C:28](Br)[CH:29]=[CH:30][CH:31]=1>>[Cl:25][C:26]1[CH:31]=[C:30]([N:6]2[CH2:5][C@:4]3([CH2:10][C@@H:9]([C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[N:8]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:7]3)[O:3][C:2]2=[O:1])[CH:29]=[CH:28][CH:27]=1
Reactant: Clc1cccc(Br)c1
Reactant: CC(C)(C)OC(=O)[C@@H]1CC2(CNC(=O)O2)CN1C(=O)OC(C)(C)C
Product: CC(C)(C)OC(=O)[C@@H]1C[C@]2(CN(c3cccc(Cl)c3)C(=O)O2)CN1C(=O)OC(C)(C)C
Yield: 21.7 %

Procedure:
Following the procedure from Example 1 step C using (8S)-di-tert-butyl 2-oxo-1-oxa-3,7-diazaspiro[4.4]nonane-7,8-dicarboxylate (2) (189 mg, 0.55 mmol, 1 eq.) and 3-chloro bromobenzene (60 μl, 0.55 mmol, 1 eq.) gave 54 mg (119) of (5R,8S)-di-tert-butyl 3-(3-chlorophenyl)-2-oxo-1-oxa-3,7-diazaspiro[4.4]nonane-7,8-dicarboxylate (A4). 1H NMR (300 MHz, DMSO) 7.68 (m, 1H), 7.55-7.38 (m, 2H), 7.2 (m, 1H), 4.38-4.28 (m, 1H), 4.2-4.05 (m, 2H), 3.75-3.6 (m, 2H), 2.7-2.4 (m, 2H), 1.4 (m, 18H).
Reaction SMILES: [NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1>O1CCOCC1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[N:3]([CH3:24])[C:4](=[O:23])[C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:31]4[CH:30]=[CH:29][CH:28]=[C:27]([O:26][CH3:25])[CH:32]=4)[CH:14]=3)[O:9][CH:8]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7]2)[N:6]=1
Reactant: CN1C(=O)C2(CC(c3ccccc3)Oc3ccc(Br)cc32)N=C1N
Reactant: COc1cccc(B(O)O)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Product: COc1cccc(-c2ccc3c(c2)C2(CC(c4ccccc4)O3)N=C(N)N(C)C2=O)c1
Temperature: 120 °C
Yield: 7.9 %

Procedure:
Pd(PPh3)2Cl2 (5 mg, 0.01 mmol) in a 10 mL of flask under Ar was treated sequentially with 2′-amino-6-bromo-1′-methyl-2-phenylspiro[chroman-4,4′-imidazol]-5′(1′H)-one (20 mg, 0.052 mmol) in 1,4-dioxane (1 mL), Cs2CO3 (2 N, 0.3 mL) and 3-methoxyphenylboronic acid (16 mg, 0.104 mmol). The mixture was heated under 120° C. under Ar using microwave for 30 minutes. The reaction mixture was concentrated in vacuo to give the residue, which was purified preparative TLC and HPLC to give 2′-amino-6-(3-methoxyphenyl)-1′-methyl-2-phenylspiro[chroman-4,4′-imidazol]-5′(1′H)-one (1.69 mg, 8%). 1H-NMR (MeOD): 2.05 (m, 1H), 2.21 (m, 1H), 3.06 (m, 3H), 3.72 (s, 3H), 5.19 (m, 0.3H), 5.81 (m, 0.7H), 6.76 (m, 1H), 6.91 (m, 2H), 6.97 (m, 1H), 7.08 (m, 1H), 7.21 (m, 1H), 7.26 (m, 1H), 7.33 (m, 2H), 7.39 (m, 2H), 7.57 (m, 1H).
Reaction SMILES: [C:1]([C:3]1[CH:19]=[CH:18][C:6]([C:7]([NH:9][CH2:10][CH2:11][CH2:12][C:13]([O:15]CC)=[O:14])=[O:8])=[CH:5][CH:4]=1)#[N:2].Br[CH2:21][CH2:22][CH2:23][O:24][CH3:25]>>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:7]([N:9]([CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])[CH2:21][CH2:22][CH2:23][O:24][CH3:25])=[O:8])=[CH:18][CH:19]=1)#[N:2]
Reactant: COCCCBr
Reactant: CCOC(=O)CCCNC(=O)c1ccc(C#N)cc1
Product: COCCCN(CCCC(=O)O)C(=O)c1ccc(C#N)cc1

Procedure:
Using ethyl 4-(4-cyanobenzamido)butanoate and 1-bromo-3-methoxypropane, and by the reaction and purification in the same manner as in the method described in Step 2 of Example 28, 4-(4-cyano-N-(3-methoxypropyl)benzamido)butanoic acid was obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[N+:13]([C:16]1[CH:21]=[CH:20][C:19](O)=[CH:18][CH:17]=1)([O-:15])=[O:14]>C1COCC1.C(N(CC)CC)C.CN(C1C=CN=CC=1)C>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:8]([O:10][C:19]2[CH:20]=[CH:21][C:16]([N+:13]([O-:15])=[O:14])=[CH:17][CH:18]=2)=[O:9])=[CH:11][CH:12]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(Oc1ccc([N+](=O)[O-])cc1)c1ccc([N+](=O)[O-])cc1
Temperature: -30 °C
Reaction time: 1 h
Yield: 76.4 %

Procedure:
8.77 g of 4-nitrobenzoic acid (52.5 mM) were dissolved in 400 ml of THF and 53.1 g of triethylamine (525.0 mM). The solution was cooled to −30° C. and 6.01 g of methansulfochloride (52.5 mM) were added dropwise. The mixture was stirred for 1 h at this temperature, then 6.95 g of 4-nitrophenol (50.0 mM) were added at once, followed by 250 mg of DMAP. The reaction mixture was stirred for 1 h at −30° C. and was allowed to warm to room temperature while stirred overnight. The next day, the reaction mixture was filtered, the cake was washed with THF and the filtrate was evaporated to dryness. The residue was purified by chromatography using silica gel and dichloromethane to give 11.0 g (38.2 mM, 76%) of 4-nitrophenyl 4-nitrobenzoate as white crystals.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]=1[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][C:16]=1OC=C)(=[O:3])[CH3:2].O>CO.C1COCC1>[C:1]([O:4][C:5]1[C:6]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)=[C:7]2[C:12](=[CH:13][CH:14]=1)[CH:11]=[CH:10][CH:9]=[CH:8]2)(=[O:3])[CH3:2]
Reactant: C=COc1ccc2ccccc2c1-c1c(OC(C)=O)ccc2ccccc12
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: CC(=O)Oc1ccc2ccccc2c1-c1cccc2ccccc12
Temperature: 0 °C
Reaction time: 10 h
Yield: 34 %

Procedure:
30.4 mg (0.086 mmol) of 2-acetyloxy-2′-vinyloxy1,1′-binaphthyl and 2.8 mg (0.004 mmol) of Co (OAc) (L3) were dissolved in 90 μl of a mixed solvent (2:1) of methanol and THF under the atmosphere and 8 μl (0.44 mmol) of water was added to the mixture, and the mixture was then stirred at 0° C. After 10 hours, the reaction solution was analyzed by HPLC, to find that 66% of the 2-acetyloxy-2′-vinyloxy1,1′-binaphthyl was left with an optical purity of 44% ee. Further, the reaction solution was purified by silica gel column chromatography to obtain the reaction product O-acetylbinaphthol in a yield of 34%. Also, the kre1 value showing the selectivity of reactions at this time was 20.7.
Reaction SMILES: [C:1]([OH:12])(=O)/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH3:13][N:14]([CH3:23])[CH2:15][CH2:16][CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1>>[C:1]([CH:21]1[CH2:22][CH:17]([CH2:16][CH2:15][N:14]([CH3:13])[CH3:23])[CH2:18][CH2:19][NH:20]1)(=[O:12])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CN(C)CCC1CCNCC1
Reactant: CCCCCCC/C=C/C(=O)O
Product: CCCCCCC/C=C/C(=O)C1CC(CCN(C)C)CCN1

Procedure:
The same procedures as in Example 2 were carried out using (E)-2-decenoic acid and 4-(2-dimethylaminoethyl)piperidine as starting raw materials, to produce an intended compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:13]([C:14]([OH:16])=O)=[C:12]([CH3:17])[NH:11][C:10](=[O:18])[NH:9]2)[CH:5]=[CH:6][CH:7]=1.[C:19]1([CH:25]=[CH:26][CH2:27][NH:28][CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:13]([C:14]([N:28]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH2:27][CH:26]=[CH:25][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[O:16])=[C:12]([CH3:17])[NH:11][C:10](=[O:18])[NH:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC1=C(C(=O)O)C(c2cccc(Cl)c2)NC(=O)N1
Reactant: COC(=O)CNCC=Cc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN(C)C=O
Product: COC(=O)CN(CC=Cc1ccccc1)C(=O)C1=C(C)NC(=O)NC1c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
320 mg (1.20 mmol) of 4-(3-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid was dissolved in 2 ml of DMF. 280 mg (1.20 mmol) of methyl (3-phenyl-2-propene-1-ylamino)acetate and 276 mg (1.44 mmol) of WSC hydrochloride were added to the obtained solution, and they were stirred at room temperature overnight. After the extraction with ethyl acetate, the extract was dried over magnesium sulfate. Ethyl acetate was evaporated under reduced pressure. The residue was purified by the silica gel chromatography (methylene chloride/methanol=200/1 to 50/1) to obtain the title compound.
Reaction SMILES: Cl[C:2]1[CH:19]=[CH:18][C:5]2[C:6](=[O:17])[C:7]3[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:8]=3[CH2:9][CH2:10][C:4]=2[CH:3]=1.[F:20][C:21]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:22]=1[NH2:23].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C1(C)C=CC=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2].C(O)(C)(C)C>[F:20][C:21]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:22]=1[NH:23][C:2]1[CH:19]=[CH:18][C:5]2[C:6](=[O:17])[C:7]3[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:8]=3[CH2:9][CH2:10][C:4]=2[CH:3]=1
Reactant: COc1ccc2c(c1)C(=O)c1ccc(Cl)cc1CC2
Reactant: Nc1ccc(F)cc1F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: CC(C)(C)O
Solvent: Cc1ccccc1
Product: COc1ccc2c(c1)C(=O)c1ccc(Nc3ccc(F)cc3F)cc1CC2
Yield: 87 %

Procedure:
In accordance with general method AA, 0.50 g (1.8 mmol) of 2-chloro-7-methoxy-10,11-dihydrodibenzo[a,d]-cyclohepten-5-one (34), 0.25 g (1.9 mmol) of 2,4-difluoroaniline, 0.05 g (0.22 mmol) of Pd(OAc)2, 0.10 g (0.21 mmol) of 2-(dicyclohexylphosphino)-2′-,4′-,6′-triisopropyl-biphenyl, 0.70 g (6.2 mmol) of K—O-tert-butylate, 5 ml of toluene and 1 ml of tert-BuOH are used. Reaction time: 1 h. Purification is carried out via flash chromatography (SiO2, hexane/ethyl acetate 8+2). Yield: 87%; melting point: 123-126° C. (decomposition)
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[S:10](=[O:12])(=[O:11])[C:9]2[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=2[S:7]1(=[O:18])=[O:17].[N:19]1[CH:24]=[CH:23][CH:22]=[N:21][C:20]=1[N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.O>CN(C=O)C>[N:19]1[CH:24]=[CH:23][CH:22]=[N:21][C:20]=1[N:25]1[CH2:30][CH2:29][N:28]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]2[S:10](=[O:12])(=[O:11])[C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[S:7]2(=[O:18])=[O:17])[CH2:27][CH2:26]1
Reactant: O=S1(=O)c2ccccc2S(=O)(=O)N1CCCCBr
Reactant: c1cnc(N2CCNCC2)nc1
Solvent: O
Solvent: CN(C)C=O
Product: O=S1(=O)c2ccccc2S(=O)(=O)N1CCCCN1CCN(c2ncccn2)CC1
Temperature: 0 °C

Procedure:
0.028 mol of 2-(4-bromobutyl)-1,3,2-benzodithiazole 1,1,3,3-tetroxide and 0.056 mol of 1-(2-pyrimidinyl)piperazine in 125 ml of absolute DMF are stirred at 250° C. for 6 hours. The mixture is then cooled to 0° C., 150 ml of water are added dropwise with stirring, and the substance which has crystallised out is filtered off with suction. The product is purified by chromatography on silic gel; the eluting agent is ethyl acetate.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11](=O)[C:12]([O-:14])=[O:13])=[CH:2]1.[As](=O)([O-])([O-])[O-].[Na+].[Na+].[Na+].C(N(CC(O)=O)CC(O)=O)C[N:26](CC(O)=O)CC(O)=O.B([O-])([O-])[O-].B([O-])([O-])[O-].B([O-])([O-])[O-].B([O-])([O-])[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]>>[NH2:26][C@@H:11]([C:12]([OH:14])=[O:13])[CH2:10][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1
Reactant: O=C([O-])C(=O)Cc1c[nH]c2ccccc12
Reactant: O=C(O)CN(CCN(CC(=O)O)CC(=O)O)CC(=O)O
Agent: O=[As]([O-])([O-])[O-]
Agent: [Na+]
Agent: [O-]B([O-])[O-]
Product: N[C@H](Cc1c[nH]c2ccccc12)C(=O)O

Procedure:
The extent of reaction was followed by measuring the amount of indole-3-pyruvate formed using the following assay: to 5 μl, 10 μl and 20 μl of reaction mix, 200 μl of the following solution was added: 0.5 mM sodium arsenate; 0.5 mM EDTA; and 50 mM sodium tetraborate (pH 8.5). Absorbance of the indole-3-pyruvate enol-borate complex at 325 nm was compared to a standard curve of indole-3-pyruvate prepared in the same solution.
Reaction SMILES: [N+:1]([C:4]1[CH:21]=[CH:20][C:7]([CH2:8][NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:22](OC(=O)C)(=[O:24])[CH3:23]>N1C=CC=CC=1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][CH:12]=2)[C:22](=[O:24])[CH3:23])=[CH:20][CH:21]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(CNCc2ccc([N+](=O)[O-])cc2)cc1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)N(Cc1ccc([N+](=O)[O-])cc1)Cc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.1 %

Procedure:
To a solution of bis(4-nitrobenzyl)amine (500 mg, 1.741 mmol) in pyridine (9 mL) was slowly added acetic anhydride (0.18 mL, 1.92 mmol) via syringe. The resulting mixture was stirred at rt for 2 hours, and the reaction was concentrated in vacuo. The residue was dissolved in toluene and evaporated to dryness in vacuo. The residue was dissolved in 19:1 EtOAc:methanol, washed with water and brine, dried (Na2SO4), filtered and concentrated to afford the title compound (551 mg, 96%). MS (APCI) m/z 330.2 (M+H)+.