Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)=[CH:5][CH:4]=1.C(S)CC.[H-].[K+]>CN(C)C=O>[S:10]1[CH:11]=[CH:12][CH:13]=[C:9]1[C:6]1[CH:7]=[CH:8][C:3]([OH:2])=[CH:4][CH:5]=1
Reactant: COc1ccc(-c2cccs2)cc1
Agent: CCCS
Agent: [H-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Oc1ccc(-c2cccs2)cc1

Procedure:
To a solution of 8.80 g (2-(4-methoxyphenyl)thiophene (prepared from 2-thienylmagnesium bromide and p-iodoanisole) and 5.4 ml propanethiol in 100 ml dry dimethylformamide was carefully added 7.00 g 35% potassium hydride in mineral oil. The reaction mixture was heated at reflux under nitrogen for 16 hours. Isolation of the resulting product afforded after crystallization 2.42 g 4-(2-thienyl)phenol as a yellow powder.
Reaction SMILES: [NH2:1][CH:2]([CH:5]([CH3:7])[CH3:6])[C:3]#[N:4].C(N(CC)CC)C.[Cl:15][C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][N:24]=1)[C:19](Cl)=[O:20].O>C(Cl)Cl.C(OCC)(=O)C>[C:3]([CH:2]([NH:1][C:19](=[O:20])[C:18]1[CH:22]=[CH:23][N:24]=[C:16]([Cl:15])[CH:17]=1)[CH:5]([CH3:7])[CH3:6])#[N:4]
Reactant: O=C(Cl)c1ccnc(Cl)c1
Reactant: CC(C)C(N)C#N
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)C(C#N)NC(=O)c1ccnc(Cl)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 84.1 %

Procedure:
2.0 g (0.02 mol) of 2-amino-3-methylbutyronitrile and 2.8 ml (0.02 mol) of triethylamine were dissolved in 30 ml of methylene chloride. The solution was cooled to 10° C. or below and 3.0 g (0.017 mol) of 2-chloroisonicotinoyl chloride was added dropwise thereto at 10° C. or below lest unfavorable heat generation should occur. Then, the mixture was stirred at room temperature for 1.5 h to conduct a reaction. Water and ethyl acetate were added thereto to conduct extraction. The extract was washed with water, dried over anhydrous sodium sulfate and concentrated to obtain an oil, which was purified according to silica gel column chromatography to obtain 3.4 g (yield: 84.1%) of the intended product in the form of a colorless oil.
Reaction SMILES: [C:1]([CH2:3][C:4]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[CH:9][C:5]=1[C:6](O)=[O:7])#[N:2].[NH2:15][C:16]1[CH:20]=[CH:19][NH:18][N:17]=1>C(O)(=O)C>[CH3:14][O:13][C:11]1[CH:12]=[C:4]2[C:5](=[CH:9][CH:10]=1)[C:6](=[O:7])[NH:2][C:1]([NH:15][C:16]1[CH:20]=[CH:19][NH:18][N:17]=1)=[CH:3]2
Reactant: COc1ccc(C(=O)O)c(CC#N)c1
Reactant: Nc1cc[nH]n1
Solvent: CC(=O)O
Product: COc1ccc2c(=O)[nH]c(Nc3cc[nH]n3)cc2c1
Temperature: 130 °C
Reaction time: 1 h
Yield: 87.4 %

Procedure:
2-Cyanomethyl-4-methoxy-benzoic acid (1.91 g, 0.01 mol), 3-amino-pyrazole (1 g, 0.01 mol) and acetic acid (15 ml) were sealed in a bottle (20 ml). The mixture was heated at 130° C. for 20 minutes under microwave irradiation. The mixture was concentrated and the residue was dissolved in 5 ml MeOH. The solution was added dropwise to 200 ml water. After stirred for 1 hour, solid was collected and dried to give product (2.24 g, 82% yield). LC-MS:
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[BrH:12]>>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([Br:12])=[CH:4][N:3]=1
Reactant: Br
Reactant: Brc1nccc2ccccc12
Product: Brc1cnc(Br)c2ccccc12

Procedure:
The starting material was prepared by reaction of 1-bromoisoquinoline with HBr to give 1,4-dibromoisoquinoline, m.p. 95°-96°, followed by reaction of this compound with trimethyloxonium tetrafluoroborate in CH2Cl2 to give 1,4-dibromo-2-methylisoquinolinium tetrafluoroborate; n.m.r. in solvent A: 3.5(s, 3H); 7.2-8.4(m, 5H).
Reaction SMILES: Cl.[Cl:2][CH2:3][CH2:4][NH2:5].Cl.[Cl:7][C:8]1[CH:17]=[C:16]2[C:11]([C:12]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=3)=[CH:13][N:14]=[N:15]2)=[CH:10][CH:9]=1>>[Cl:7][C:8]1[CH:17]=[C:16]2[C:11]([C:12]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([S:25]([NH:5][CH2:4][CH2:3][Cl:2])(=[O:26])=[O:27])=[CH:23][CH:24]=3)=[CH:13][N:14]=[N:15]2)=[CH:10][CH:9]=1
Reactant: O=S(=O)(Cl)c1ccc(Nc2cnnc3cc(Cl)ccc23)cc1
Reactant: NCCCl
Agent: Cl
Product: O=S(=O)(NCCCl)c1ccc(Nc2cnnc3cc(Cl)ccc23)cc1

Procedure:
This compound is prepared in a similar manner to the procedure of Example 10 using equimolar quantities of 2-chloroethylamine hydrochloride instead of 3-chloropropylamine hydrochloride and 4-(7-chloro-4-cinnolinylamino)benzenesulphonyl chloride hydrochloride instead of 4-(7-chloro-4-quinolinylamino) benzenesulphonyl chloride.
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][C@H:7]([C:11]([O:13]C)=[O:12])[CH2:6]1.Cl[C:16]1[N:21]=[C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:19]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:18][N:17]=1>CN(C)C=O>[C:22]1([C:20]2[C:19]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:18][N:17]=[C:16]([O:3][CH2:4][C@@H:5]3[CH2:10][CH2:9][CH2:8][C@H:7]([C:11]([OH:13])=[O:12])[CH2:6]3)[N:21]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: Clc1ncc(-c2ccccc2)c(-c2ccccc2)n1
Reactant: COC(=O)[C@H]1CCC[C@@H](CO)C1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(O)[C@H]1CCC[C@@H](COc2ncc(-c3ccccc3)c(-c3ccccc3)n2)C1
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 15.1 %

Procedure:
94 mg (2.34 mmol) of sodium hydride (suspension in oil) were added to a solution of 178 mg (1.03 mmol) of methyl (1S,3R)-3-hydroxymethylcyclohexanecarboxylate in 5 ml of dimethylformamide at 0° C. After 30 minutes, a solution of 250 mg (0.94 mmol) of 2-chloro-4,5-diphenylpyrimidine in 2 ml of dimethylformamide was added. The reaction mixture was allowed to reach room temperature and was then heated at 60° C. for 2 hours. The solvent was concentrated under high vacuum and the residue was mixed with water and dichloromethane. After acidification with 1 N HCl, the aqueous phase was extracted with dichloromethane, dried and concentrated. The crude mixture was purified on silica gel with heptane/ethyl acetate (gradient 0% to 25% in 40 minutes, then isocratic for 20 minutes). 55 mg (15%) of the desired product were obtained.
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:12]=[N:13][CH:14]=[C:15]([N:17]4[CH2:22][CH2:21][NH:20][C@@H:19]([CH2:23][C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:18]4)[N:16]=3)[CH:9]=2)[NH:4][N:3]=1.C=O.[C:32]([BH3-])#N>C(O)(=O)C>[CH2:23]([C@@H:19]1[N:20]([CH3:32])[CH2:21][CH2:22][N:17]([C:15]2[N:16]=[C:11]([C:8]3[CH:9]=[C:10]4[C:5](=[CH:6][CH:7]=3)[NH:4][N:3]=[C:2]4[CH3:1])[N:12]=[N:13][CH:14]=2)[CH2:18]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: [BH3-]C#N
Reactant: Cc1n[nH]c2ccc(-c3nncc(N4CCN[C@@H](Cc5ccccc5)C4)n3)cc12
Agent: C=O
Solvent: CC(=O)O
Product: Cc1n[nH]c2ccc(-c3nncc(N4CCN(C)[C@@H](Cc5ccccc5)C4)n3)cc12
Temperature: 25 °C
Reaction time: 5 h
Yield: 50 %

Procedure:
To a solution of 5-[(S)-3-benzylpiperazin-1-yl]-3-(3-methylindazol-5-yl)-[1,2,4]triazine 12 (14 mg, 0.036 mmol.) in 10% methanolic acetic acid was added 37% aqueous formaldehyde solution (0.06 mL, 0.74 mmol.) and cyanoborohydride resin (2.42 equiv./g, 44 mg, 0.11 mmol.). The reaction mixture was stirred at room temperature for 5 hours. The reaction mixture was filtered and the filtrate was evaporated under reduced pressure. The crude product was purified by RP-HPLC to yield the desired 5-[(S)-3-benzyl-4-methyl-piperazin-1-yl]-3-(3-methylindazol-5-yl)-[1,2,4]triazine 28 (7.1 mg, 0.018 mmol.).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[N:19]1[C:28]2[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=2[CH:22]=[CH:21][CH:20]=1.C[Si]([N:33]=[C:34]=[S:35])(C)C.Cl>C1C=CC=CC=1.O>[N:19]1[C:28]2[CH:27]([C:34](=[S:35])[NH2:33])[CH2:26][CH2:25][CH2:24][C:23]=2[CH:22]=[CH:21][CH:20]=1
Reactant: C[Si](C)(C)N=C=S
Reactant: c1cnc2c(c1)CCCC2
Agent: Cl
Agent: [Li]CCCC
Solvent: c1ccccc1
Solvent: CC(C)NC(C)C
Solvent: CCCCCC
Product: NC(=S)C1CCCc2cccnc21
Reaction time: 1 h
Yield: 30 %

Procedure:
A solution of di-isopropylamine (33.3g, 0.33 mol) in benzene (150 ml) was cooled in ice and treated with 9% w/v butyl-lithium in hexane (237 ml, 0.33 mol). After 45 minutes the solution was treated with 5,6,7,8-tetrahydroquinoline (39.9 g, 0.3 mol) dropwise with stirring. After 1.5 hours trimethylsilyl-isothiocyanate (43.2 ml. 0.3 mol) was added and the resulting solution was allowed to stand at 0° C for 0.5 hours and at room temperature for 1 hour. Water (50 ml.) was added and the resulting mixture acidified with 2N HCl. The acid solution was separated, washed with ethyl acetate and the pH was adjusted to 9 with solid sodium carbonate. Extraction with chloroform followed by drying of the extract over MgSO4, filtration and evaporation gave a thick gum which crystallised on trituration with n-hexane. Recrystallisation from methanol gave 5,6,7,8-tetrahydroquinoline-8-thiocarboxamide (16g, 30%) m.p. 160°. The hydrochloride was prepared by dissolution of the free base in hot iso-propyl alcohol adding ethereal HCl solution and allowing to crystallise. m.p. 263-4°.
Reaction SMILES: [CH2:1]([SH:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[Na].[CH3:15][C:16]1([CH3:63])[CH2:21][CH:20]([N:22]([C:33]2[N:38]=[C:37]([N:39]([CH:50]3[CH2:55][C:54]([CH3:57])([CH3:56])[NH:53][C:52]([CH3:59])([CH3:58])[CH2:51]3)[CH:40]3[CH2:45][C:44]([CH3:47])([CH3:46])[NH:43][C:42]([CH3:49])([CH3:48])[CH2:41]3)[N:36]=[C:35](Cl)[N:34]=2)[CH:23]2[CH2:28][C:27]([CH3:30])([CH3:29])[NH:26][C:25]([CH3:32])([CH3:31])[CH2:24]2)[CH2:19][C:18]([CH3:62])([CH3:61])[NH:17]1>C1(C)C(C)=CC=CC=1>[CH3:58][C:52]1([CH3:59])[CH2:51][CH:50]([N:39]([C:37]2[N:38]=[C:33]([N:22]([CH:23]3[CH2:28][C:27]([CH3:30])([CH3:29])[NH:26][C:25]([CH3:32])([CH3:31])[CH2:24]3)[CH:20]3[CH2:21][C:16]([CH3:15])([CH3:63])[NH:17][C:18]([CH3:62])([CH3:61])[CH2:19]3)[N:34]=[C:35]([S:13][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[N:36]=2)[CH:40]2[CH2:41][C:42]([CH3:48])([CH3:49])[NH:43][C:44]([CH3:46])([CH3:47])[CH2:45]2)[CH2:55][C:54]([CH3:57])([CH3:56])[NH:53]1
Reactant: CC1(C)CC(N(c2nc(Cl)nc(N(C3CC(C)(C)NC(C)(C)C3)C3CC(C)(C)NC(C)(C)C3)n2)C2CC(C)(C)NC(C)(C)C2)CC(C)(C)N1
Reactant: CCCCCCCCCCCCS
Agent: [Na]
Solvent: Cc1ccccc1C
Product: CCCCCCCCCCCCSc1nc(N(C2CC(C)(C)NC(C)(C)C2)C2CC(C)(C)NC(C)(C)C2)nc(N(C2CC(C)(C)NC(C)(C)C2)C2CC(C)(C)NC(C)(C)C2)n1

Procedure:
Following the procedure described in Example 11 and using 20.3 g (0.11 mol) of 1-dodecanthiol, 2.53 g (0.11 mol) of sodium and 70.25 g (0.1 mol) of 2,4-bis[N,N-bis(2,2,6,6-tetramethyl-4-piperidyl)amino]-6-chloro-1,3,5-triazine in 250 ml of xylene, the product of melting point 168°-170° C. is obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][S:10]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19]C)=[O:18])=[CH:15][CH:14]=2)(=[O:12])=[O:11])=[CH:5][CH:4]=1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:23]([N:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[S:10]([C:13]1[CH:14]=[CH:15][C:16]([C:17]([OH:19])=[O:18])=[CH:21][CH:22]=1)(=[O:12])=[O:11])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: BrCc1ccccc1
Reactant: COC(=O)c1ccc(S(=O)(=O)Nc2ccc(OC)cc2)cc1
Product: COc1ccc(N(Cc2ccccc2)S(=O)(=O)c2ccc(C(=O)O)cc2)cc1

Procedure:
Prepared as in example 5-10 from Methyl 4-(N-(4-methoxyphenyl)sulfamoyl)-benzoate (example 5-35a) and benzyl bromide MS (M−H, 396); 1H NMR (400 MHz, DMSO-d6): δ, ppm: 3.66 (s, 3H), 4.75 (s, 2H), 6.76 (d, J=8 Hz, 2H), 6.90 (d, J=8 Hz, 2H), 7.23 (m, 5H), 7.74 (d, J=8 Hz, 2H), 8.11 (d, J=8 Hz, 2H), 13.51 (s, 1H).
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][C@@:5]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[O:10][C:9](=[O:11])[N:8]([C@H:12]([C:14]2[CH:19]=[CH:18][C:17]([CH:20]=[CH2:21])=[CH:16][CH:15]=2)[CH3:13])[CH2:7][CH2:6]1.[OH2:28].O=O>CN(C=O)C.CCOC(C)=O.[Cu]Cl.[Pd](Cl)Cl>[C:20]([C:17]1[CH:16]=[CH:15][C:14]([C@@H:12]([N:8]2[CH2:7][CH2:6][C@:5]([CH2:4][CH2:3][CH2:2][OH:1])([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[O:10][C:9]2=[O:11])[CH3:13])=[CH:19][CH:18]=1)(=[O:28])[CH3:21]
Reactant: O
Reactant: C=Cc1ccc([C@H](C)N2CC[C@](CCCO)(c3ccccc3)OC2=O)cc1
Agent: Cl[Cu]
Agent: Cl[Pd]Cl
Agent: O=O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(=O)c1ccc([C@H](C)N2CC[C@](CCCO)(c3ccccc3)OC2=O)cc1
Yield: 52 %

Procedure:
A round-bottom flask was charged with copper(I) chloride (49 mg, 0.5 mmol), and a solution of (R)-6-(3-hydroxypropyl)-6-phenyl-3-((S)-1-(4-vinylphenyl)ethyl)-1,3-oxazinan-2-one (80 mg, 0.2 mmol) in DMF (3 mL) was added, followed by H2O (0.5 mL) and palladium(II) chloride (18 mg, 0.1 mmol). The reaction mixture was vigorously stirred under a balloon of oxygen at rt overnight. The reaction was diluted with EtOAc (5 mL), and filtered. The filtrate was separated, and the aqueous layer was extracted with EtOAc (3×). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to give the crude product, which was purified by preparative TLC to afford (R)-3-((S)-1-(4-acetylphenyl)ethyl)-6-(3-hydroxypropyl)-6-phenyl-1,3-oxazinan-2-one (40 mg, 52%). 1H NMR (CDCl3): 1.34 (m, 1H), 1.49 (m, 3H), 1.68 (m, 1H), 1.92 (m, 2H), 2.11-2.27 (m, 3H), 2.46 (s, 3H), 2.84 (m, 2H), 3.51 (m, 2H), 5.64 (m, 1H), 6.86 (m, 2H), 7.26 (m, 6H), 7.51 (m, 2H).
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([CH3:19])[CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:12]=1)(=O)=O.[C-:22]#[N:23].[K+]>O1CCOCC1.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>[C:22]([C:7]1[CH:8]=[C:9]([CH3:19])[CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:12]=1)#[N:23]
Reactant: Cc1cc(OS(=O)(=O)C(F)(F)F)cc(-c2ccccc2)c1
Reactant: [C-]#N
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [K+]
Solvent: C1COCCO1
Product: Cc1cc(C#N)cc(-c2ccccc2)c1
Yield: 20 %

Procedure:
A mixture of 3-trifluoromethanesulfonyloxy-5-phenyltoluene (35.6 g; 0.128 mol), tetrakis(triphenylphosphine)palladium (12 g; 0.01 mol) and KCN (15.11 g; 0.23 mol) in dioxan (300 ml) was heated at reflux under argon an atmosphere for 24 hours. After extraction with ether and evaporating, the residue was purified by flash chromatography eluting with petroleum ether/ethyl acetate (84/6) to give 3-cyano-5-phenyltoluene. Yield=20%.
Reaction SMILES: Br[C:2]1[C:3](=[O:32])[C:4]2[C:9]([C:10]=1[C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=1)=[CH:8][CH:7]=[C:6]([O:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][N:25]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:24][CH2:23]1)[CH:5]=2.O1CCN(CCOC2C=C3C(C(C4C=CC=CC=4)=C(Br)C3=O)=CC=2)CC1.[F:59][C:60]1[CH:61]=[C:62](B(O)O)[CH:63]=[CH:64][C:65]=1[O:66][CH3:67]>>[F:59][C:60]1[CH:61]=[C:62]([C:2]2[C:3](=[O:32])[C:4]3[C:9]([C:10]=2[C:11]2[CH:12]=[C:13]([F:18])[CH:14]=[C:15]([F:17])[CH:16]=2)=[CH:8][CH:7]=[C:6]([O:19][CH2:20][CH2:21][N:22]2[CH2:23][CH2:24][N:25]([S:28]([CH3:31])(=[O:29])=[O:30])[CH2:26][CH2:27]2)[CH:5]=3)[CH:63]=[CH:64][C:65]=1[O:66][CH3:67]
Reactant: CS(=O)(=O)N1CCN(CCOc2ccc3c(c2)C(=O)C(Br)=C3c2cc(F)cc(F)c2)CC1
Reactant: COc1ccc(B(O)O)cc1F
Agent: O=C1C(Br)=C(c2ccccc2)c2ccc(OCCN3CCOCC3)cc21
Product: COc1ccc(C2=C(c3cc(F)cc(F)c3)c3ccc(OCCN4CCN(S(C)(=O)=O)CC4)cc3C2=O)cc1F
Yield: 71 %

Procedure:
The procedure of Step 7 of Example 1 was repeated except for using 2-bromo-3-(3,5-difluorophenyl)-6-{2-[4-(methylsulfonyl)piperazin-1-yl]ethoxy}-1H-inden-1-one obtained in Step 1 of Example 96 as a starting material instead of 6-(2-morpholinoethoxy)-2-bromo-3-phenyl-1H-inden-1-one, 3-fluoro-4-methoxyphenylboronic acid instead of 3-pyridinylboronic acid, and being purified by silica gel column chromatography (EtOAc/CH2Cl2=1:1) to obtain the title compound (71%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[OH:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.C(#N)C.C(=O)([O-])[O-].[Na+].[Na+]>O.CN(C=O)C.Cl[Pd-2](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>[OH:19][C:20]1[CH:25]=[C:24]([C:2]2[CH:3]=[C:4]3[C:10]([C:11]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[O:12])=[CH:9][NH:8][C:5]3=[N:6][CH:7]=2)[CH:23]=[CH:22][CH:21]=1
Reactant: OB(O)c1cccc(O)c1
Reactant: O=C(c1ccccc1)c1c[nH]c2ncc(Br)cc12
Agent: Cl[Pd-2](Cl)([PH](c1ccccc1)(c1ccccc1)c1ccccc1)[PH](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CC#N
Solvent: O
Product: O=C(c1ccccc1)c1c[nH]c2ncc(-c3cccc(O)c3)cc12
Reaction time: 0.33 h
Yield: 70.5 %

Procedure:
To (5-bromo-1H-pyrrolo[2,3-b]pyridine-3-yl)-phenyl-methanone (50 mg, 0.167 mmol), 3-hydroxyphenyl boronic acid (30 mg, 0.217 mmol), and dichlorobis (triphenylphosphino)palladium (II) (6 mg, 0.0083 mmol) in a Smith process vial was added 1 mL of a 1:1 mixture of acetonitrile, and a 2 M solution of sodium carbonate in water. The reaction was run in a Personal Chemistry® microwave reactor at 150° C. for 1200 s. The mixture was diluted with DMF (ca. 5 mL) and filtered on a silica plug. The filtrate was adsorbed on silica gel. Purification on silica gel with a gradient of MeOH/dichloromethane afforded [5-(3-hydroxy-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-yl]-phenyl-methanone as a yellow solid (37 mg, 71% yield). 1H NMR (500 MHz, DMSO-d6) δ 6.80 (dd, J=2.0, 7.5 Hz, 1H), 7.10 (t, J=2.0 Hz, 1H), 7.14 (d, J=9.0 Hz, 1H), 7.31 (t, J=7.5 Hz, 1H), 7.57 (t, J=7.5 Hz, 2H), 7.65 (t, J=7.5 Hz, 1H), 7.84 (d, J=7.0 Hz, 2H), 8.14 (s, 1H), 8.61 (d, J=2.0 Hz, 1H), 8.68 (d, J=2.0 Hz, 1H), 9.65 (broad s, 1H). MS: m/z 315 (M+H+).
Reaction SMILES: [Br-].[Li+].[F:3][C:4]([F:16])([C:9]1([C:12]([F:15])([F:14])[F:13])[CH2:11][O:10]1)[C:5]([F:8])([F:7])[F:6].[C:17](=[O:19])=[O:18]>CN1CCCC1=O>[C:17]1(=[O:18])[O:10][CH2:11][C:9]([C:12]([F:15])([F:14])[F:13])([C:4]([F:16])([F:3])[C:5]([F:8])([F:7])[F:6])[O:19]1
Reactant: FC(F)(F)C(F)(F)C1(C(F)(F)F)CO1
Reactant: O=C=O
Agent: [Br-]
Agent: [Li+]
Solvent: CN1CCCC1=O
Product: O=C1OCC(C(F)(F)F)(C(F)(F)C(F)(F)F)O1
Temperature: 100 °C
Yield: 72 %

Procedure:
73 mL N-methylpyrrolidone (NMP) was introduced into a 500-mL autoclave; 1.5 g (17 mmol) lithium bromide and 132 g (575 mmol) 2-pentafluoroethyl-2-trifluoromethyloxirane were charged; and the interior of the system was replaced with CO2 5 times. The reaction solution was heated to 100° C. and pressurization with CO2 at 0.8 MPa was performed until the starting epoxide had disappeared. After the reaction was finished, the reaction solution was returned to room temperature; quenching was performed with 300 mL 1 N aqueous hydrochloric acid; separation was carried out and the organic layer was dried over magnesium sulfate; and suction filtration was performed. The filtrate was subjected to rectification under reduced pressure using a 10-stage Oldershaw column to obtain 113 g (isolated yield=72%, purity=99.7%) 1-trifluoromethyl-1-pentafluoroethylethylene carbonate (=4-pentafluoroethyl-4-trifluoromethyl-1,3-dioxolan-2-one). Molecular Sieve 3A (Wako Pure Chemical Industries, Ltd.) was then introduced and the water content was reduced to 30 ppm.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH:28]([O:32][CH2:33][CH3:34])[O:29][CH2:30][CH3:31])=[C:5]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:6]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-:22])=[O:21])[CH:15]=2)[C:7]=1[C:8]([O:10][CH2:11][CH2:12]Cl)=[O:9].[CH2:35]([NH:37][CH2:38][CH3:39])[CH3:36]>C(O)CC.[I-].[Na+]>[CH3:1][C:2]1[NH:3][C:4]([CH:28]([O:32][CH2:33][CH3:34])[O:29][CH2:30][CH3:31])=[C:5]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:6]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-:22])=[O:21])[CH:15]=2)[C:7]=1[C:8]([O:10][CH2:11][CH2:12][N:37]([CH2:38][CH3:39])[CH2:35][CH3:36])=[O:9]
Reactant: CCNCC
Reactant: CCOC(=O)C1=C(C(OCC)OCC)NC(C)=C(C(=O)OCCCl)C1c1cccc([N+](=O)[O-])c1
Agent: [I-]
Agent: [Na+]
Solvent: CCCO
Product: CCOC(=O)C1=C(C(OCC)OCC)NC(C)=C(C(=O)OCCN(CC)CC)C1c1cccc([N+](=O)[O-])c1
Yield: 114.5 %

Procedure:
A mixture of 2-chloroethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-diethoxymethyl-1,4-dihydropyridine-3-carboxylate (2.0 g), diethylamine (1.75 g) and sodium iodide (60.3 mg) in n-propylalcohol (4 ml) was refluxed for 17 hours. After removal of the solvent from the reaction mixture, water and ethyl acetate were added to the residue. The ethyl acetate layer was washed twice with water, dried over magnesium sulfate, and concentrated to give a brown oil (2.46 g) of 2-(N,N-diethylamino)ethyl 2-methyl-4-(3-nitrophenyl)-5-ethoxycarbonyl-6-diethoxymethyl-1,4-dihydropyridine-3-carboxylate, which was identified by converting to the corresponding 6-formyl compound (oil) and then to the corresponding 6-cyano compound, m.p. 150° to 152° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][NH2:25])=[O:23])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Cl.[C:27](=N)(N)[CH3:28]>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[C:27]([CH3:28])=[N:25][NH:24][C:22]4=[O:23])=[CH:17][CH:16]=3)[CH2:13][CH2:14]2)=[CH:7][CH:8]=1
Reactant: CC(=N)N
Reactant: COc1ccc(N2CCN(c3ccc(NC(=O)NN)cc3)CC2)cc1
Agent: Cl
Solvent: CN(C)C=O
Product: COc1ccc(N2CCN(c3ccc(-n4c(C)n[nH]c4=O)cc3)CC2)cc1
Temperature: 130 °C

Procedure:
A mixture of 53 parts of N-{4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl}hydrazinecarboxamide, 53 parts of ethanimidamide hydrochloride and 135 parts of N,N-dimethylformamide is stirred and heated for 3 hours at 130° C. The reaction mixture is cooled and poured onto water. The precipitated product is filtered off, washed with water and with methanol, and crystallized from N,N-dimethylformamide. The product is filtered off and recrystallized from 1,4-dioxane, yielding 19.5 parts of 2,4-dihydro-4-{4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl}-5-methyl-3H-1,2,4-triazol-3-one; 298.4° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[C:15]2[C:6]([NH:7][CH:8]=[C:9]2[CH2:10][CH2:11][N:12]([CH3:14])[CH3:13])=[CH:5][CH:4]=1>[Pd].Cl>[CH3:13][N:12]([CH2:11][CH2:10][CH:9]1[C:15]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:16]=2)[NH:7][CH2:8]1)[CH3:14]
Reactant: COc1ccc2[nH]cc(CCN(C)C)c2c1
Agent: [Pd]
Agent: Cl
Product: COc1ccc2c(c1)C(CCN(C)C)CN2
Yield: 45.4 %

Procedure:
A mixture of 5-methoxy-N,N-dimethyltryptamine (0.200 g, 0.939 mmol) and palladium on carbon (10%, 200 mg) in 50 M aqueous HCl (50 ml) was hydrogenated at 50 psi overnight. The catalyst was removed by filtration, and the filtrate was extracted with dichloromethane (3×25 ml). The combined organic extracts were evaporated in vacuo and the residue was purified by flash chromatography (silica gel, CH2Cl2—MeOH—NH3(aq); 92:8:0.8) to give 94 mg (47%) of the title compound; δH (250 MHz, CDCl3) 1.71 (1H, m), 1.99 (1H, m), 2.26 (6H, s), 2.37 (2H, m), 3.20 (1H, t, J=8.0 Hz), 3.27 (1H, m), 3.68 (1H, t, J=8.0 Hz), 3.75 (3H, s), 6.60-6.61 (2H, m), 6.73 (1H, m).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:29])[CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])[CH:20]=[CH:21][CH:22]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.[C:30]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1O)(=[O:32])[CH3:31]>>[C:30]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[O:29][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[CH:18]=[C:19]([NH:23][C:24](=[O:28])[CH:25]([CH3:26])[CH3:27])[CH:20]=[CH:21][CH:22]=2)[CH2:13][CH2:12]1)(=[O:32])[CH3:31]
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCC(O)c3ccc(F)cc3)CC2)c1
Reactant: CC(=O)c1ccccc1O
Product: CC(=O)c1ccccc1OC(CCN1CCC(c2cccc(NC(=O)C(C)C)c2)CC1)c1ccc(F)cc1

Procedure:
Prepared by Procedure A and Scheme AN using N-(3-{1-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 2-acetylphenol: ESMS m/e: 517.1 (M+H)+.