Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:8]=[C:7]2[S:9][C:10]3[CH2:15][S:14](=[O:16])[CH2:13][CH2:12][C:11]=3[C:6]2=[C:5]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[C:4]=1[Cl:25]>CO>[NH2:1][CH2:2][C:3]1[N:8]=[C:7]2[S:9][C:10]3[CH2:15][S@@:14](=[O:16])[CH2:13][CH2:12][C:11]=3[C:6]2=[C:5]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[C:4]=1[Cl:25]
Reactant: COc1ccc(-c2c(Cl)c(CN)nc3sc4c(c23)CCS(=O)C4)cc1
Solvent: CO
Product: COc1ccc(-c2c(Cl)c(CN)nc3sc4c(c23)CC[S@](=O)C4)cc1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To methanol heated to 60° C. (63 L) was added 2-(aminomethyl)-3-chloro-4-(4-methoxyphenyl)-7-oxido-5,8-dihydro-6H-thiopyrano[4′,3′:4,5]thieno[2,3-b]pyridine (6.5 kg) and the mixture was stirred for 5 minutes, followed by addition of (R)-(−)-hydrogenphosphate-1,1′-bihaphthyl-2,2′-diyl (3.455 kg). The mixture was stirred at 60° C. for 10 minutes, slowly cooled to 25° C. After stirring for 1 hours, crystals were filtered off and washed with methanol (13L). Methanol-ethanol (1:3, 63 L) was heated to 75° C. and the resultant crystals were added thereto. The mixture was slowly cooled to 25° C. and stirred for 1 hours. Crystals deposited were filtered off and washed with methanol-ethanol (1:1, 13 L). The crystals were dissolved in tetrahydrofuran-water (3:1, 121. 4 L) and active carbon (242 g) was added thereto. The mixture was stirred at room temperature for 15 minutes and the active carbon was filtered off. The tetrahydrofuran layer was distilled off under reduced pressure and the resultant aqueous layer was stirred at 25° C. to deposit crystals. The crystals were filtered off to obtain a diastereomer salt of (S)-2-(aminomethyl)-3-chloro-4-(4-methoxyphenyl)-7-oxido-5,8-dihydro-6H-thiopyrano[4′,3′:4,5]thieno[2,3-b]pyridine with (R)-(−)-hydrogenphosphate-1,1′-binaphthyl-2,2′-diyl (4.618 kg, 37.7%). 1H-NMR (DMSO-d6) δ: 1.98-2.04 (1H, m), 2.35-2.43 (1H, m), 2.71-2.81 (1H, m), 3.01-3.06 (1H, m), 3.83 (3H, s), 3.18 (1H, d, J=17.1 Hz), 4.26 (1H, d, J=17.1 Hz), 4.35 (2H, s), 0.07-7.43 (12H, m), 7.96-8.10 (4H, m), 8.64 (3H, bs).
Reaction SMILES: CS[C:3]([S:9][CH3:10])=[C:4]([C:7]#[N:8])[C:5]#[N:6].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].N1C=CC=CC=1>C(O)(C)C>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:3]([S:9][CH3:10])=[C:4]([C:7]#[N:8])[C:5]#[N:6])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]
Reactant: CSC(SC)=C(C#N)C#N
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: c1ccncc1
Solvent: CC(C)O
Product: CSC(=C(C#N)C#N)N1CCN(C(=O)OC(C)(C)C)CC1

Procedure:
With the exclusion of air, 7.22 g (42.4 mmol) of 3,3-bis(methylsulfanyl)-2-cyano-acrylonitrile (Maybridge), 7.90 g (42.4 mmol) of piperazine-N-carboxylic acid tert-butyl ester (Aldrich; Milwaukee/USA) and 0.24 g (3 mmol) of pyridine are heated to boiling in 75 ml of isopropanol for 4 hours. Cooling, concentration by evaporation and drying under a high vacuum yield 3-(4-tert-butoxycarbonyl-piperazin-1-yl)-3-methylsulfanyl-2-cyano-acrylonitrile; C14H20N4SO2: calc. C54.52%, H 6.54%, N 18.17%, S 10.40%; found C54.37%, H 6.50%, N 17.85%, S 10.25%.
Reaction SMILES: [NH2:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([O:8][CH2:9][CH:10]=[CH2:11])=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.C1COCC1.[C:26]12([C:36]3[CH:37]=[C:38]([CH:42]=[CH:43][C:44]=3[O:45][CH2:46][O:47][CH2:48][CH2:49][O:50][CH3:51])[C:39](Cl)=[O:40])[CH2:35][CH:30]3[CH2:31][CH:32]([CH2:34][CH:28]([CH2:29]3)[CH2:27]1)[CH2:33]2>O>[C:26]12([C:36]3[CH:37]=[C:38]([CH:42]=[CH:43][C:44]=3[O:45][CH2:46][O:47][CH2:48][CH2:49][O:50][CH3:51])[C:39]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH:10]=[CH2:11])=[O:7])=[CH:12][CH:13]=3)=[O:40])[CH2:27][CH:28]3[CH2:29][CH:30]([CH2:31][CH:32]([CH2:34]3)[CH2:33]1)[CH2:35]2
Reactant: COCCOCOc1ccc(C(=O)Cl)cc1C12CC3CC(CC(C3)C1)C2
Reactant: C=CCOC(=O)c1ccc(N)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: O
Product: C=CCOC(=O)c1ccc(NC(=O)c2ccc(OCOCCOC)c(C34CC5CC(CC(C5)C3)C4)c2)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
700 mg (3.95 mmol) of allyl 4-aminobenzoate, 1 ml (4.3 mmol) of triethylamine and 50 ml of THF were introduced into a round-bottomed flask. A solution of 1.5 g (3.96 mmol) of 3-(1-adamantyl)-4-methoxyethoxymethoxybenzoyl chloride was added dropwise and the mixture was stirred at room temperature for 4 hours. The reaction medium was poured into water and extracted with ethyl ether. The organic phase was separated out after settling had taken place, dried over magnesium sulfate and evaporated. The residue obtained was purified by chromatography on a column of silica, eluted with dichloromethane. 1.7 g (83%) of the expected allylic ester was recovered in the form of an oil.
Reaction SMILES: [CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([CH:23]([NH2:25])[CH3:24])[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][C:6]([CH3:26])=[N:5]1)([CH3:3])[CH3:2].[O-:27][C:28]#[N:29].[K+]>C(O)(=O)C.O>[CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([CH:23]([NH:25][C:28]([NH2:29])=[O:27])[CH3:24])[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][C:6]([CH3:26])=[N:5]1)([CH3:3])[CH3:2]
Reactant: N#C[O-]
Reactant: Cc1nc(-c2nc3c(s2)CCOc2cc(C(C)N)ccc2-3)n(C(C)C)n1
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: Cc1nc(-c2nc3c(s2)CCOc2cc(C(C)NC(N)=O)ccc2-3)n(C(C)C)n1
Temperature: 50 °C
Reaction time: 8 h
Yield: 4.1 %

Procedure:
To a solution of 1-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-ethylamine (0.120 g, 0.325 mmol) in acetic acid (0.0923 mL) and water (3.45 mL) was added a solution of potassium cyanate (0.132 g, 0.00162 mol) in Water (1.0 mL, 0.056 mol) dropwise. The reaction was stirred at 50° C. overnight, cooled down, filtered, and rinsed with cold water. The crude was precipitated in methanol/water and repurified by reverse-phase HPLC to give 542 as a beige solid (5.5 mg). MS (ESI+) 413.1. 1H NMR (400 MHz, DMSO) δ 8.27 (d, J=8.2 Hz, 1H), 7.12 (dd, J=8.3, 1.5 Hz, 1H), 6.98 (d, J=1.4 Hz, 1H), 6.47 (d, J=8.2 Hz, 1H), 5.83-5.68 (m, 1H), 5.47 (s, 2H), 4.70 (p, J=7.1 Hz, 1H), 4.44-4.25 (m, 2H), 3.42 (t, J=4.9 Hz, 2H), 2.32 (s, 3H), 1.52 (dd, J=6.5, 1.6 Hz, 6H), 1.32 (d, J=7.0 Hz, 3H)
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([S:9]([NH:12][CH2:13][CH2:14][NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.[C:23]1([C:29]2[N:34]=[CH:33][C:32]([C:35](O)=[O:36])=[CH:31][N:30]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(CCCN=C=NCC)C>CN(C)C=O.C(OCC)(=O)C>[C:23]1([C:29]2[N:34]=[CH:33][C:32]([C:35]([NH:1][CH2:2][C:3]3[CH:4]=[C:5]([S:9]([NH:12][CH2:13][CH2:14][NH:15][C:16](=[O:22])[O:17][C:18]([CH3:19])([CH3:21])[CH3:20])(=[O:10])=[O:11])[CH:6]=[CH:7][CH:8]=3)=[O:36])=[CH:31][N:30]=2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: O=C(O)c1cnc(-c2ccccc2)nc1
Reactant: CC(C)(C)OC(=O)NCCNS(=O)(=O)c1cccc(CN)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CC(C)(C)OC(=O)NCCNS(=O)(=O)c1cccc(CNC(=O)c2cnc(-c3ccccc3)nc2)c1
Reaction time: 2.5 h
Yield: 84.1 %

Procedure:
To a mixture consisting of tert-butyl 2-(3-(aminomethyl)phenylsulfonamido)ethylcarbamate (Compound 16, 278 mg), 2-phenylpyrimidine-5-carboxylic acid (Compound 17; synthesis described in Example 1, Steps 1-3 of WO 2007/041634 to Aldous et al., entitled “Pyrimidine Amide Compounds as PGDS Inhibitors”; 182 mg), HOBt (123 mg), and N-methyl-morpholine (0.11 mL) in N,N-dimethylformamide (11 mL) was added 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (287 mg) and the mixture was stirred for 2.5 hours. The crude reaction mixture was diluted with ethyl acetate and washed with brine. The organic phase was dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by silica chromatography (5:95 methanol-dichloromethane) to afford the title intermediate (363 mg, 87%); MS (ESI−) m/z 510 (M−1).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[C:10]([C:11]([F:14])([F:13])[F:12])[C:3]=12.[N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[C:17](B(O)O)[CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>O1CCOCC1.O>[F:12][C:11]([F:14])([F:13])[C:10]1[C:3]2[C:4](=[N:5][CH:6]=[CH:7][C:2]=2[C:17]2[CH:16]=[N:15][C:24]3[C:19]([CH:18]=2)=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:8][N:9]=1
Reactant: FC(F)(F)c1n[nH]c2nccc(Cl)c12
Reactant: OB(O)c1cnc2ccccc2c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1COCCO1
Product: FC(F)(F)c1n[nH]c2nccc(-c3cnc4ccccc4c3)c12
Temperature: 100 °C
Reaction time: 3 h
Yield: 33.1 %

Procedure:
A [1,1-bis-(diphenylphosphino)-ferrocene]dichloropalladium(II) dichloromethane complex (0.74 g) was added to a solution of compound (1c) (2.0 g), quinoline-3-boronic acid (2.5 g), and an aqueous sodium carbonate solution (1 M, 18 mL) in 1,4-dioxane (45 mL) under a nitrogen atmosphere, followed by stirring at 100° C. for 3 hr. The reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. After distillation of the solvent, the residue was purified by neutral silica gel column chromatography (chloroform/methanol) to obtain compound (1d) (0.94 g, 33%) as a white solid.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:16]=[CH:15][C:14]([CH:17]([CH3:19])[CH3:18])=[CH:13][C:5]=1[O:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].C(N(CC)CC)C.[C:27]([C:29]1[CH:30]=[CH:31][C:32]([O:39][CH3:40])=[C:33]([S:35](Cl)(=[O:37])=[O:36])[CH:34]=1)#[N:28]>O1CCCC1.O>[C:27]([C:29]1[CH:30]=[CH:31][C:32]([O:39][CH3:40])=[C:33]([S:35]([NH:1][CH2:2][CH2:3][C:4]2[CH:16]=[CH:15][C:14]([CH:17]([CH3:18])[CH3:19])=[CH:13][C:5]=2[O:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:37])=[O:36])[CH:34]=1)#[N:28]
Reactant: COc1ccc(C#N)cc1S(=O)(=O)Cl
Reactant: CCOC(=O)COc1cc(C(C)C)ccc1CCN
Solvent: CCN(CC)CC
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)COc1cc(C(C)C)ccc1CCNS(=O)(=O)c1cc(C#N)ccc1OC
Temperature: 25 °C
Reaction time: 6 h
Yield: 72.5 %

Procedure:
To a stirred solution of 326 mg of ethyl [2-(2-amino-ethyl)-5-isopropylphenoxy]acetate hydorochloride and 0.452 mL of triethylamine in a mixture of 10 mL of tetrahydrofuran and 5 mL of water was added 238 mg of 5-cyano-2-methoxybenzene-sulfonyl chloride under ice-cooling, and the mixture was stirred at room temperature for 6 hours. To the reaction mixture was added 30 mL of water, and the mixture was extracted with 120 mL of ethyl acetate. The organic layer was washed with 100 mL of water, and 100 mL of brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: ethyl acetate-hexane) to give 343 mg of ethyl [2-[2-(5-cyano-2-methoxybenzenesulfonylamino)ethyl]-5-isopropylphenoxy]acetate.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([CH2:18][NH:19][CH:20]3[C:28]4[C:23](=[C:24]([O:29][CH3:30])[CH:25]=[CH:26][CH:27]=4)[CH2:22][CH2:21]3)[O:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:31](OC(=O)C)(=[O:33])C>C(O)=O>[CH:31]([N:19]([CH:20]1[C:28]2[C:23](=[C:24]([O:29][CH3:30])[CH:25]=[CH:26][CH:27]=2)[CH2:22][CH2:21]1)[CH2:18][C:9]1[O:10][C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]=1)=[O:33]
Reactant: CC(=O)OC(C)=O
Reactant: COc1cccc2c1CCC2NCc1nc(-c2ccccc2)c(-c2ccccc2)o1
Solvent: O=CO
Product: COc1cccc2c1CCC2N(C=O)Cc1nc(-c2ccccc2)c(-c2ccccc2)o1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of 1-(4,5-diphenyloxazol-2-yl)methylamino-2,3-dihydro-4-methoxy-1H-indene (0.13 g) in formic acid (5 ml) was added acetic anhydride (1 ml) at 0° C. After being stirred for 5 hours at room temperature, the solvent was evaporated in vacuo. The residue was partitioned between ethyl acetate and 1N hydrochloric acid. The organic layer was washed with water, sat. NaHCO3, and brine. The dried solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel to give l-[N-formyl-N-[(4,5-diphenyloxazol-2-yl)methyl]amino]-2,3-dihydro-4-methoxy-1H-indene (0.12 g).
Reaction SMILES: N1(C2N=CN=C(NC3C=C(CS(N)(=O)=O)C=CC=3)N=2)CCCCC1.Cl[C:26]1[N:31]=[CH:30][N:29]=[C:28]([NH:32][C:33]2[CH:34]=[C:35]([CH2:39][S:40]([NH2:43])(=[O:42])=[O:41])[CH:36]=[CH:37][CH:38]=2)[N:27]=1.[OH:44][CH2:45][CH:46]1[CH2:51][NH:50][CH2:49][CH2:48][NH:47]1>>[OH:44][CH2:45][CH:46]1[CH2:51][NH:50][CH2:49][CH2:48][N:47]1[C:26]1[N:31]=[CH:30][N:29]=[C:28]([NH:32][C:33]2[CH:34]=[C:35]([CH2:39][S:40]([NH2:43])(=[O:42])=[O:41])[CH:36]=[CH:37][CH:38]=2)[N:27]=1
Reactant: OCC1CNCCN1
Reactant: NS(=O)(=O)Cc1cccc(Nc2ncnc(Cl)n2)c1
Agent: NS(=O)(=O)Cc1cccc(Nc2ncnc(N3CCCCC3)n2)c1
Product: NS(=O)(=O)Cc1cccc(Nc2ncnc(N3CCNCC3CO)n2)c1

Procedure:
B13 was prepared following the procedure reported for B1 using A1 and rac-2-(hydroxymethyl)piperazine. MS (ES) C15H21N7O3S requires: 379. found: 380 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[C:7]2[N:8]=[C:9]([CH3:11])[S:10][C:6]=2[CH:5]=[CH:4][C:3]=1[CH:12](O)[CH3:13].C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:27]=[N+:28]=[N-:29].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[N:27]([CH:12]([C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9]([CH3:11])=[N:8][C:7]=2[C:2]=1[Br:1])[CH3:13])=[N+:28]=[N-:29]
Reactant: Cc1nc2c(Br)c(C(C)O)ccc2s1
Reactant: [N-]=[N+]=[N-]
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1nc2c(Br)c(C(C)N=[N+]=[N-])ccc2s1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a mixture of 1-(4-bromo-2-methyl-1,3-benzothiazol-5-yl)ethanol (1.81 g, 6.65 mmol) in methylene chloride (40 mL) was added triethylamine (1.39 mL, 9.98 mmol), followed by methanesulfonyl chloride (0.643 mL, 8.31 mmol). After stirring at room temperature for 30 minutes, the resultant mixture was diluted with dichloromethane, washed with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and then concentrated to dryness under reduced pressure. The crude mesylate was dissolved in N,N-dimethylformamide (20 mL) and treated with sodium azide (2.16 g, 33.2 mmol) at room temperature overnight. After diluting with ethyl acetate, the mixture was washed with water and brine, dried over magnesium sulfate, and evaporated to dryness. The crude product was used in next step (1.90 g, 96%). LCMS calculated for C10H10BrI\T4S(M+H)+: m/z=297.0; found: 297.0.
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([C:5]2[O:6][C:7]([CH2:10][C:11]3[S:12][C:13]4[CH:19]=[C:18]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[CH:17]=[CH:16][C:14]=4[N:15]=3)=[N:8][N:9]=2)[CH2:2]1.[CH:26](=O)[C:27]([CH3:30])([CH3:29])[CH3:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>ClCCl.C(O)(=O)C>[CH2:26]([N:1]1[CH2:4][CH:3]([C:5]2[O:6][C:7]([CH2:10][C:11]3[S:12][C:13]4[CH:19]=[C:18]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[CH:17]=[CH:16][C:14]=4[N:15]=3)=[N:8][N:9]=2)[CH2:2]1)[C:27]([CH3:30])([CH3:29])[CH3:28]
Reactant: CC(C)(C)C=O
Reactant: c1ccc(-c2ccc3nc(Cc4nnc(C5CNC5)o4)sc3c2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Solvent: ClCCl
Product: CC(C)(C)CN1CC(c2nnc(Cc3nc4ccc(-c5ccccc5)cc4s3)o2)C1
Yield: 42.2 %

Procedure:
Compound 42a (117 mg, 0.34 mmol), pivalaldehyde (57.8 mg, 0.67 mmol), sodium triacetoxyborohydride (27.4 mg, 0.13 mmol), and acetic acid (0.123 μl, 2.15 μmol) were stirred in dichloromethane (0.05 mL) at rt for 24 h. H2O was added, followed by CH2Cl2. The organic layer was separated, dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by preparative HPLC (HPLC method D) to give Compound 42b (60 mg, 43% yield) as a tan film. LCMS ESI 419.1 (M+MeOH+H), RT=1.80 min (Method B). 1H NMR (500 MHz, CD3OD-d4) d 8.25 (d, J=1.65 Hz, 1H), 7.97-8.05 (m, 1H), 7.81 (dd, J=1.93, 8.53 Hz, 1H), 7.64-7.73 (m, 2H), 7.42-7.53 (m, 2H), 7.30-7.41 (m, 1H), 4.64-4.92 (m, 5H), 4.34-4.53 (m, 2H), 3.22-3.29 (m, 2H), 1.06 (s, 9H).
Reaction SMILES: [C:1]([C:3]([C:11]1[S:12][C:13]([C:16]#[N:17])=[CH:14][CH:15]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:5][CH2:6]I)#[N:2].[F:18][C:19]([F:36])([F:35])[C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[N:24][CH:25]=1>>[C:1]([C:3]([C:11]1[S:12][C:13]([C:16]#[N:17])=[CH:14][CH:15]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:5][CH2:6][N:32]1[CH2:33][CH2:34][N:29]([CH2:28][CH2:27][O:26][C:23]2[CH:22]=[CH:21][C:20]([C:19]([F:36])([F:18])[F:35])=[CH:25][N:24]=2)[CH2:30][CH2:31]1)#[N:2]
Reactant: FC(F)(F)c1ccc(OCCN2CCNCC2)nc1
Reactant: CC(C)C(C#N)(CCCI)c1ccc(C#N)s1
Product: CC(C)C(C#N)(CCCN1CCN(CCOc2ccc(C(F)(F)F)cn2)CC1)c1ccc(C#N)s1

Procedure:
The title compound was synthesized in accordance with Example 77 from 4-cyano-4-(5-cyano-2-thienyl)-5-methylhexyl iodide and 1-[2-(5-trifluoromethyl-2-pyridyloxy)ethyl]piperazine. The physico-chemical data of the compound was as below.
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:15][C:16]1[CH:40]=[CH:39][C:38]([CH:41]2[CH2:46][CH2:45][N:44](C(OC(C)(C)C)=O)[CH2:43][CH2:42]2)=[CH:37][C:17]=1[C:18]([NH:20][C:21]1[CH:30]=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:28]=[CH:27][C:22]=1[C:23]([O:25][CH3:26])=[O:24])=[O:19])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(Cl)(Cl)Cl>[CH2:8]([O:15][C:16]1[CH:40]=[CH:39][C:38]([CH:41]2[CH2:42][CH2:43][NH:44][CH2:45][CH2:46]2)=[CH:37][C:17]=1[C:18]([NH:20][C:21]1[CH:30]=[C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:28]=[CH:27][C:22]=1[C:23]([O:25][CH3:26])=[O:24])=[O:19])[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(C2CCN(C(=O)OC(C)(C)C)CC2)ccc1OCc1ccccc1
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(C2CCNCC2)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.1 %

Procedure:
Trifluoroacetic acid (1.0 mL) was added to a chloroform (2.0 mL) solution of the obtained methyl 2-(2-(benzyloxy)-5-(1-(tert-butoxycarbonyl)piperidin-4-yl)benzamido)-4-phenylbenzoate (0.19 g), followed by stirring at room temperature for 1 hour and 30 minutes. The solvent was evaporated under reduced pressure, and water was added to the residue. After adjusting the pH to 7.4 with a saturated aqueous solution of sodium bicarbonate, chloroform was added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 0.15 g of methyl 2-(2-(benzyloxy)-5-(piperidin-4-yl)benzamido)-4-phenylbenzoate as a white solid.
Reaction SMILES: [CH:1]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.[CH2:9]=[CH2:10]>>[CH2:9]=[CH:10][CH2:1][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH:3]=[CH2:2]
Reactant: C=C
Reactant: C1=CCCCCCC1
Product: C=CCCCCCCC=C

Procedure:
A mixture of cyclooctene and ethylene was contacted with catalyst and adjuvant as in Examples IX and X at room temperature and 25 psi pressure to yield 13 weight percent 1,9-decadiene. This shows that ethylene and a cyclic olefin are converted to an acyclic polyene.
Reaction SMILES: [F:1][CH:2]([F:11])[C:3](=O)[CH2:4][C:5](OCC)=[O:6].C(O)=O.[CH3:15][NH:16][NH2:17]>C(OC)(C)(C)C>[F:1][CH:2]([F:11])[C:3]1[CH:4]=[C:5]([OH:6])[N:16]([CH3:15])[N:17]=1
Reactant: CNN
Reactant: CCOC(=O)CC(=O)C(F)F
Solvent: O=CO
Solvent: COC(C)(C)C
Product: Cn1nc(C(F)F)cc1O
Temperature: 5 °C
Reaction time: 20 h
Yield: 99.9 %

Procedure:
166 g (1 mol) of ethyl 4,4-difluoro-3-oxobutanoate were charged in 500 ml of methyl tert-butyl ether and treated with 140 g of formic acid. After cooling of the mixture to 5° C., 119 g (as 40% aqueous solution) of monomethylhydrazine were added. The mixture was then stirred for 20 h at 22° C. The phases were separated, and the organic phase was washed with 200 ml of water and dried over MgSO4. After the removal of the solvent under reduced pressure, 148 g of the product was obtained as an yellow solid having an m.p. of 133° C. and a purity of 95%. Yield 95%.
Reaction SMILES: [Na].C[O-].[Na+].[CH:5](OCC)=[O:6].[S:10]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[C:13](=[O:20])[CH2:12][CH2:11]1>C1C=CC=CC=1.CO>[OH:6][CH:5]=[C:12]1[C:13](=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[S:10][CH2:11]1
Reactant: CCOC=O
Reactant: O=C1CCSc2ccccc21
Agent: C[O-]
Agent: [Na+]
Agent: [Na]
Solvent: c1ccccc1
Solvent: CO
Product: O=C1C(=CO)CSc2ccccc21
Reaction time: 8 h

Procedure:
From 9.2 g of sodium (0.4 mol) and 160 ml of absolute methanol there is prepared sodium methanolate. Then the surplus of methanol is evaporated in vacuo and 200 ml of dry benzene and 32.6 g of ethyl formate (0.44 mol) are added to the dry residue. While stirring and passing nitrogen through the mixture, there are added 32.8 g of 2,3-dihydro-4H-1-benzothiopyran-4-one, dissolved in 160 ml of dry benzene dropwise to it to keep the reaction temperature in the range from 0° to 50° C. All components become dissolved and after that, the sodium salt of the 2,3-dihydro-3-(hydroxymethylene)-4H-1-benzothiopyran-4-one precipitates. After allowing the reaction mixture to stand overnight at room temperature, 400 ml of water are added for dissolving the sodium salt. The aqueous layer is separated from the organic solvent and, after agitating twice with ether and treatment with charcoal, it is acidified with half-concentrated aqueous hydrochloric acid. The oily title compound is extracted with chloroform, dried with sodium sulphate and after evaporation of the solvent, distilled in vacuo. b.p. 0.3 mm, 134°-138°; yield: 32.9 g (85.6%).
Reaction SMILES: FC(F)(F)C([O-])=O.[CH3:8][O:9][C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[CH:19]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:20][C:21]([NH:23][CH3:24])=O)[NH:12][N:11]=1.FC(F)(F)C(O)=O.N1C2C(=CC=CC=2C(C2C=CC=CC=2)CCNC)C=C1>>[CH3:8][O:9][C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][C:17]=2[CH:19]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:20][CH2:21][NH:23][CH3:24])[NH:12][N:11]=1
Reactant: CNC(=O)CC(c1ccccc1)c1cccc2[nH]nc(OC)c12
Agent: CNCCC(c1ccccc1)c1cccc2cc[nH]c12
Agent: O=C([O-])C(F)(F)F
Solvent: O=C(O)C(F)(F)F
Product: CNCCC(c1ccccc1)c1cccc2[nH]nc(OC)c12

Procedure:
[3-(3-Methoxy-1H-indazol-4-yl)-3-phenyl-propyl]-methyl-amine CXC was prepared as a trifluoroacetate from 3-(3-methoxy-1H-indazol-4-yl)-N-methyl-3-phenyl-propionamide and trifluoroacetic acid, using the procedure described for prepration of [3-(1H-Indol-7-yl)-3-phenyl-propyl]-methyl-amine XX (Example 4). MS (M+H)=297.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7]O)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:30]N1C(=O)CCC1=O>C1COCC1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][Br:30])=[CH:4][CH:3]=1
Reactant: OCCc1ccc(Cl)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Clc1ccc(CCBr)cc1
Yield: 54.5 %

Procedure:
A stirred solution of 4-chlorophenethyl alcohol (131 g) and triphenylphosphine (241.3 g) in dry THF (500 mL) at 0° C. was treated portionwise over 30 min. with N-bromosuccinimide (163.75 g). The resulting black solution was stirred overnight at room temperature, whereupon the THF was evaporated and the residue stirred with ether. The solution was filtered to remove triphenylphosphine oxide and the filtrate evaporated and treated with hexane. The stirred mixture was filtered, evaporated, and the residue distilled under reduced pressure to give 100 g of 4-chlorophenethyl bromide as a colorless liquid, b.p. 85° C. (3 mm Hg).