Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[N:10]=[C:9]([CH:11]=O)[S:8][C:6]=2[N:7]=1.[NH:19]1[CH2:22][CH:21]([N:23]2[CH2:28][CH2:27][S:26](=[O:30])(=[O:29])[CH2:25][CH2:24]2)[CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[N:10]=[C:9]([CH2:11][N:19]3[CH2:22][CH:21]([N:23]4[CH2:28][CH2:27][S:26](=[O:30])(=[O:29])[CH2:25][CH2:24]4)[CH2:20]3)[S:8][C:6]=2[N:7]=1
Reactant: O=Cc1nc2c(N3CCOCC3)nc(Cl)nc2s1
Reactant: O=S1(=O)CCN(C2CNC2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: O=S1(=O)CCN(C2CN(Cc3nc4c(N5CCOCC5)nc(Cl)nc4s3)C2)CC1
Reaction time: 65 h
Yield: 89 %

Procedure:
A mixture of 5-chloro-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidine-2-carbaldehyde (400 mg, 1.40 mmol), 4-azetidin-3-ylthiomorpholine-1,1-dioxide (321 mg, 1.69 mmol) and 4 Å powdered molecular sieves (600 mg) in DCE (20 mL) was stirred at room temperature for 4 h before the addition of sodium triacetoxyborohydride (595 mg, 2.80 mmol). The reaction mixture was stirred for 65 h then filtered through celite, washing with DCM. The organic phase was washed with brine (×1) and concentrated in vacuo affording 5-Chloro-2-[3-(1,1-Dioxo-1-thiomorpholin-4-yl)azetidin-1-ylmethyl]-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine as an orange powder (572 mg, 89%). LCMS (Method H): RT 2.43 min [M+H]+ 459.2
Reaction SMILES: Cl.[CH3:2][C:3]1[O:4][C:5]2[C:14]3[CH:13]([CH2:15][CH2:16][NH2:17])[CH2:12][CH2:11][C:10]=3[CH:9]=[CH:8][C:6]=2[N:7]=1.C(N(CC)CC)C.[CH:25]1([C:28](Cl)=[O:29])[CH2:27][CH2:26]1.C(=O)([O-])O.[Na+]>O1CCCC1>[CH3:2][C:3]1[O:4][C:5]2[C:14]3[CH:13]([CH2:15][CH2:16][NH:17][C:28]([CH:25]4[CH2:27][CH2:26]4)=[O:29])[CH2:12][CH2:11][C:10]=3[CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: Cc1nc2ccc3c(c2o1)C(CCN)CC3
Reactant: O=C(Cl)C1CC1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1nc2ccc3c(c2o1)C(CCNC(=O)C1CC1)CC3
Reaction time: 0.25 h
Yield: 42.3 %

Procedure:
2-(2-Methyl-7,8-dihydro-6H-indeno[5,4-d][1,3]oxazol-8-yl)ethanamine hydrochloride (100 mg, 0.396 mmol) and triethylamine (111 μL, 0.792 mmol) were dissolved in tetrahydrofuran (4 mL), cyclopropanecarbonyl chloride (43.1 μL, 0.475 mmol) was added under ice-cooling, and the mixture was stirred for 15 min. To the reaction solution was added saturated aqueous sodium hydrogencarbonate solution, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→80/20) to give the title compound (47.6 mg, yield 42%).
Reaction SMILES: C[O:2][C:3](=[O:23])[C:4]1[C:5](=[CH:10][C:11]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=2)=[CH:12][CH:13]=1)[C:6]([O:8]C)=[O:7].[OH-].[Na+]>C(O)C>[Cl:22][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=1)[CH2:15][NH:14][C:11]1[CH:10]=[C:5]([C:6]([OH:8])=[O:7])[C:4](=[CH:13][CH:12]=1)[C:3]([OH:23])=[O:2]
Reactant: COC(=O)c1ccc(NCc2cccc(Cl)c2)cc1C(=O)OC
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1ccc(NCc2cccc(Cl)c2)cc1C(=O)O
Temperature: 25 °C
Yield: 99.1 %

Procedure:
A mixture of 4-(3-chloro-benzylamino)-phthalic acid dimethyl ester (1.10 g, 3.30 mmol) and 3N sodium hydroxide (50 mL) in ethanol (100 mL) was refluxed for one hour. The reaction mixture was cooled to room temperature, and the solvent was removed under vacuum. The residue was dissolved in water (100 mL), washed with CH2Cl2 (2×100 mL), and acidified (HCl). The resulting mixture was extracted with ethyl acetate (2×100 mL), and the organic phase was washed with water (2×100 mL), dried (MgSO4), and evaporated, providing 1.00 g of 4-(3-chloro-benzylamino)-phthalic acid, in 99% yield; 1H NMR (DMSO-d6) δ 4.37 (d, J=5.7 Hz, 2H), 6.59-6.62 (m, 2H), 7.18 (t, J=6.0 Hz, 1H), 7.28-7.39 (m, 4H), 7.56-7.61 (m, 1H), 12.51 (br, 2H).
Reaction SMILES: C(O[C:4](=[O:23])[CH:5]([C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH2:21][CH3:22])(=[O:20])=[O:19])=[CH:14][CH:13]=1)[CH2:6][CH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1)C.[CH3:24][NH:25][C:26]([NH2:28])=[O:27].C[O-].[Mg+2].C[O-].CO>C(OCC)(=O)C>[CH:7]1([CH2:6][CH:5]([C:12]2[CH:13]=[CH:14][C:15]([S:18]([CH2:21][CH3:22])(=[O:19])=[O:20])=[CH:16][CH:17]=2)[C:4]([NH:28][C:26]([NH:25][CH3:24])=[O:27])=[O:23])[CH2:8][CH2:9][CH2:10][CH2:11]1
Reactant: CCOC(=O)C(CC1CCCC1)c1ccc(S(=O)(=O)CC)cc1
Reactant: CNC(N)=O
Agent: C[O-]
Agent: [Mg+2]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCS(=O)(=O)c1ccc(C(CC2CCCC2)C(=O)NC(=O)NC)cc1
Temperature: 25 °C
Yield: 32.8 %

Procedure:
3-Cyclopentyl-2-(4-ethanesulfonyl-phenyl)-propionic acid ethyl ester (500 mg, 1.48 mmol) and methyl urea (274 mg, 3.70 mmol) were treated with a solution of magnesium methoxide in methanol (7.4 wt %, 6.5 mL, 4.43 mmol). The reaction mixture was then concentrated in vacuo to approximately one-half the volume of methanol. The resulting reaction mixture was then heated under reflux for 2 d. The reaction mixture was allowed to cool to 25° C. and then diluted with ethyl acetate (25 mL). The mixture was filtered through a pad of celite, and the celite pad was washed with ethyl acetate (50 mL). The resulting filtrate was washed with water (40 mL) then the water layer was further extracted with ethyl acetate (40 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford a colorless oil. The oil was treated with a solution of 2/1 hexanes/ethyl acetate (10 mL), and a white solid began to precipitate. The suspension was placed in the freezer to enhance crystallization. The solid was filtered to afford 1-[3-cyclopentyl-2-(4-ethanesulfonyl-phenyl)-propionyl]-3-methyl-urea (178 mg, 33%) as a white solid: mp 200-201° C.; FAB-HRMS m/e calcd for C18H26N2O4S (M+H)+367.1691, found 367.1697.
Reaction SMILES: C([O:3][C:4]([C:6]1([C:13]([O:15]CC)=[O:14])[CH2:9][CH:8]([CH2:10][CH2:11][CH3:12])[CH2:7]1)=[O:5])C.[OH-].[Na+].O.Cl>C1C=CC=CC=1>[CH2:10]([CH:8]1[CH2:9][C:6]([C:13]([OH:15])=[O:14])([C:4]([OH:5])=[O:3])[CH2:7]1)[CH2:11][CH3:12]
Reactant: CCCC1CC(C(=O)OCC)(C(=O)OCC)C1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: c1ccccc1
Product: CCCC1CC(C(=O)O)(C(=O)O)C1

Procedure:
A solution of 3-n-propylcyclobutane-1,1-dicarboxylic acid diethyl ester (100 g., 0.413 mol, prepared as described in Reference Example 2) in benzene (200 ml.) was treated with sodium hydroxide (320 g., 8.00 mol) in water (400 mol.) for 20 hours at room temperature. The reaction mixture was acidified with 6 N hydrochloric acid and extracted with diethyl ether (3×400 ml.). After concentration of the extracts under reduced pressure, the resulting crude solid was recrystallized from chloroform to give the title compound in quantitative yield, having the following physical characteristics:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[N:22]=[C:21](Cl)[C:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:19]3[Cl:33])([C:10]2[N:14]([CH3:15])[CH:13]=[N:12][CH:11]=2)[OH:9])=[CH:4][CH:3]=1.[CH3:34][O:35][CH2:36][CH2:37][OH:38].C1(C)C=CC=CC=1.[H-].[Na+]>CCOC(C)=O>[Cl:33][C:19]1[C:18]2[C:23](=[CH:24][CH:25]=[C:16]([C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)([C:10]3[N:14]([CH3:15])[CH:13]=[N:12][CH:11]=3)[OH:9])[CH:17]=2)[N:22]=[C:21]([O:38][CH2:37][CH2:36][O:35][CH3:34])[C:20]=1[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: Cn1cncc1C(O)(c1ccc(Cl)cc1)c1ccc2nc(Cl)c(-c3ccccc3)c(Cl)c2c1
Reactant: COCCO
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: COCCOc1nc2ccc(C(O)(c3ccc(Cl)cc3)c3cncn3C)cc2c(Cl)c1-c1ccccc1
Temperature: 25 °C

Procedure:
(4-Chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol (100 mg, 0.202 mmol, Example 65), 2-methoxyethanol (16.0 μL, 0.202 mmol), toluene (2 mL), and sodium hydride (60% dispersion in mineral oil, 20.2 mg, 0.505 mmol) were combined in a round bottom flask under an N2 atmosphere. The contents were heated to reflux and refluxed overnight. The reaction solution turned from a heterogeneous white mixture to slightly yellowish with a moderate amount of precipitate. The contents were cooled to room temperature then transferred to a separatory funnel with EtOAc dilution, and extracted with saturated, aqueous NH4Cl and saturated, aqueous NaHCO3 solutions. The organic phase was separated then dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel, 0-10% DCM/(10% of a 2 M NH3 MeOH in DCM)) then further purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to afford the title compound. MS (ESI): mass calcd. for C29H25Cl2N3O3, 533.1; m/z found, 534.2 [M+H]+; 1H NMR (600 MHz, CD3OD) δ ppm 8.96 (d, J=0.9 Hz, 1H), 8.19 (d, J=1.9 Hz, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.70 (dd, J=8.8, 2.2 Hz, 1H), 7.48-7.44 (m, 4H), 7.43-7.39 (m, 3H), 7.36-7.33 (m, 2H), 6.90 (d, J=1.6 Hz, 1H), 4.59-4.54 (m, 2H), 3.70 (s, 3H), 3.68-3.63 (m, 2H), 3.25 (s, 3H).
Reaction SMILES: [F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18]([CH2:20][C:21]([O:23]C(C)(C)C)=[O:22])[CH:19]=2)[CH2:10][C@H:9]1[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[C:31]([CH3:36])[CH:30]=1)=[O:7].FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[F:43][C:40]([F:41])([F:42])[C:38]1[CH:37]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:45])[F:44])[CH:39]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18]([CH2:20][C:21]([OH:23])=[O:22])[CH:19]=2)[CH2:10][C@H:9]1[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[C:31]([CH3:36])[CH:30]=1)=[O:7]
Reactant: Cc1ccc(C[C@@H]2CN(Cc3cnn(CC(=O)OC(C)(C)C)c3)CCN2C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc1C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1ccc(C[C@@H]2CN(Cc3cnn(CC(=O)O)c3)CCN2C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc1C
Yield: 101.9 %

Procedure:
A solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(tert-butoxycarbonylmethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine (425 mg) in dichloromethane (2.5 ml) was treated with trifluoroacetic acid (2.5 ml) at room temperature for 1 hour. The mixture was adjusted to pH 7.4 with aqueous sodium bicarbonate solution and evaporated under reduced pressure. The residue was washed with a mixture of dichloromethane and methanol (9:1), and the solution was evaporated under reduced pressure and purified by column chromatography on a silica gel using a mixture of methanol and chloroform (1:9) as eluent and subsequent crystallization from ethyl acetate, isopropyl ether, and hexane to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(carboxymethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine (395 mg) as a white powder.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]([C:14]([F:17])([F:16])[F:15])([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH2:9][CH2:8]2)[OH:4].[CH2:20]=[C:21]1[O:25][C:23](=[O:24])[CH2:22]1>O1CCCC1>[F:16][C:14]([F:17])([F:15])[C:3]([C:2]([F:1])([F:18])[F:19])([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:23](=[O:24])[CH2:22][C:21](=[O:25])[CH3:20])[CH2:9][CH2:8]2)[OH:4]
Reactant: OC(c1ccc2c(c1)CCN2)(C(F)(F)F)C(F)(F)F
Reactant: C=C1CC(=O)O1
Solvent: C1CCOC1
Product: CC(=O)CC(=O)N1CCc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc21
Temperature: 25 °C
Yield: 100.3 %

Procedure:
To a stirred solution of 343 g (1.25 mole) of α,α-bis(trifluoromethyl)-2,3-dihydro-1H-indole-5-methanol in 1880 ml of dry tetrahydrofuran cooled in an ice bath is added dropwise 106 g (1.26 mole) of diketene. The solution is allowed to warm to room temperature for 16 hours and then is refluxed for 30 minutes. The solvent is evaporated to give 463 g (100%) of crude α,α-bis(trifluoromethyl)-1-(1,3-dioxobutyl)-2,3-dihydro-1H-indole-5-methanol, m.p. 150°-151°.
Reaction SMILES: C(O)(C(F)(F)F)=O.[NH:8](C(OC(C)(C)C)=O)[C@H:9]([C:26]([NH:28][C@H:29]([C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46])[CH2:30][CH2:31][CH2:32][CH2:33][NH:34][C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36])=[O:27])[CH2:10][C:11]1[N:15]=[CH:14][N:13]([S:16]([C:19]2[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[CH:12]=1>C(Cl)CCl>[NH2:8][C@H:9]([C:26]([NH:28][C@H:29]([C:45]([O:47][CH2:48][C:49]1[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=1)=[O:46])[CH2:30][CH2:31][CH2:32][CH2:33][NH:34][C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36])=[O:27])[CH2:10][C:11]1[N:15]=[CH:14][N:13]([S:16]([C:19]2[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[CH:12]=1
Reactant: Cc1ccc(S(=O)(=O)n2cnc(C[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](CCCCNC(=O)OCc3ccccc3)C(=O)OCc3ccccc3)c2)cc1
Solvent: ClCCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccc(S(=O)(=O)n2cnc(C[C@H](N)C(=O)N[C@@H](CCCCNC(=O)OCc3ccccc3)C(=O)OCc3ccccc3)c2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81.9 %

Procedure:
160 ml of TFA was added to 86 g of Boc-His(Tos)-Lys(Z)-OBzl dissolved in 100 ml of ethylene chloride under cooling with ice, and the mixture was stirred at the same temperature for 30 minutes and at room temperature for an hour. The solvent and TFA were distilled off, chloroform was added to the residue, and neutralization was carried out with aqueous potassium carbonate. After the reaction mixture was washed with saturated saline, passed through silica gel and sodium sulfate anhydride columns, the solvent was distilled off. Then, methanol was added to precipitate crystals, which were filtered out and dried to obtain 61.2 g of His(Tos)-Lys(Z)-OBzl. (By this process, the product is obtained in the crystallized form).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:14]=[C:13](/[CH:15]=[CH:16]/N(C)C)[C:12]([N+:20]([O-])=O)=[CH:11][N:10]=1>C(O)(=O)C.[Zn]>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[C:9]1[CH:14]=[C:13]2[CH:15]=[CH:16][NH:20][C:12]2=[CH:11][N:10]=1
Reactant: Cc1cccc(C)c1-c1cc(/C=C/N(C)C)c([N+](=O)[O-])cn1
Agent: [Zn]
Solvent: CC(=O)O
Product: Cc1cccc(C)c1-c1cc2cc[nH]c2cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of {(E)-2-[2-(2,6-dimethyl-phenyl)-5-nitro-pyridin-4-yl]-vinyl}-dimethyl-amine (10 g, 33.6 mmol) in glacial acetic acid (150 mL), zinc dust (22 g, 336 mmol) is added and the mixture is stirred at room temperature for 1 h. Temperature is raised to 90° C. at which the mixture is maintained for another 30 min. The resultant suspension is filtered over celite and concentrated under reduced pressure to afford 5-(2,6-dimethyl-phenyl)-1H-pyrrolo[2,3-c]pyridine as a brown solid.
Reaction SMILES: CS[C:3]1[S:4]/[C:5](=[CH:9]\[C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][CH:14]=[CH:13]3)/[C:6](=[O:8])[N:7]=1.[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26][NH2:27].CCN(C(C)C)C(C)C>>[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26][NH:27][C:3]1[S:4]/[C:5](=[CH:9]\[C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][CH:14]=[CH:13]3)/[C:6](=[O:8])[N:7]=1
Reactant: NCc1ccccn1
Reactant: CSC1=NC(=O)/C(=C/c2ccc3ncccc3c2)S1
Solvent: CCN(C(C)C)C(C)C
Product: O=C1N=C(NCc2ccccn2)S/C1=C\c1ccc2ncccc2c1

Procedure:
Similar procedure as described in example 1b was used, starting from 2-methylsulfanyl-5-[1-quinolin-6-yl-meth-(Z)-ylidene]-thiazol-4-one, (pyridin-2-ylmethyl)-amine and DIEA to give 2-[(pyridin-2-ylmethyl)-amino]-5-[1-quinolin-6-yl-meth-(Z)-ylidene]-thiazol-4-one. LC-MS m/e 347 (MH+).
Reaction SMILES: Br[CH:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH:3]=O.[NH2:11][C:12]([NH2:14])=[S:13]>C(O)C>[C:5]1([C:2]2[S:13][C:12]([NH2:14])=[N:11][CH:3]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=CC(Br)c1ccccc1
Reactant: NC(N)=S
Solvent: CCO
Product: Nc1ncc(-c2ccccc2)s1
Temperature: 25 °C
Yield: 56.8 %

Procedure:
A mixture of bromo-phenyl-acetaldehyde (1 g, 5 mmol), thiourea (0.64 g, 10 mmol) and ethanol (3.5 mL) was heated to reflux overnight. The mixture was then cooled to rt and the resulting yellow precipitate filtered. The precipitate was then washed with aqueous NaHCO3 solution (10 mL) and dried. Recrystallization from 30% methanol gave 5-phenylthiazol-2-amine (500 mg, 2.84 mmol, 56.5%) as a yellow solid. Anal. Calcd. for C9H8N2S m/z 176.2, found: 177.2 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.41 (m, 3H), 7.33 (m, 2H), 7.18 (m, 1H), 7.13 (m, 2H).
Reaction SMILES: [CH2:1]([O:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]#[C:19][Si](C)(C)C)=[CH:14][C:13]=2[CH3:24])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+]>CO>[C:18]([C:15]1[CH:16]=[CH:17][C:12]([C:9]2([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:11][CH2:10]2)=[C:13]([CH3:24])[CH:14]=1)#[CH:19]
Reactant: Cc1cc(C#C[Si](C)(C)C)ccc1C1(OCc2ccccc2)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C#Cc1ccc(C2(OCc3ccccc3)CC2)c(C)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Using General Procedure E; [4-(1-benzyloxycyclopropyl)-3-methyl-phenylethynyl]-trimethylsilane (Intermediate 75, 300.0 mg, 0.95 mmnols) in methanol (6 mL) was treated with potassium carbonate (120.0 mg, 0.87 mmol) and stirred overnight at ambient temperature. The crude alkyne (185 mg, 79%) was used directly in the next reaction.
Reaction SMILES: [CH2:1]([SiH:7]([Cl:9])[Cl:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH2:10]=[CH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]>C(O)(C)C>[CH2:1]([Si:7]([CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH3:10])([Cl:9])[Cl:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: C=CCCCCCCCCCC
Reactant: CCCCCC[SiH](Cl)Cl
Solvent: CC(C)O
Product: CCCCCCCCCCCC[Si](Cl)(Cl)CCCCCC
Temperature: 50 °C
Reaction time: 15 h

Procedure:
The above-mentioned n-hexyldichlorosilane in an amount of 3.33 g (18 millimol), 3.36 g (20 millimol) of 1-dodecene and as a catalyst a solution of H2PtCl6 ·6H2O in isopropanol (0.05 mol % relative to dichlorosilane) were charged in a flask equipped with a cooler and the mixture was reacted with stirring in an oil bath at 50° C. for 15 hours. After reaction, reaction solution was distilled to obtain n-hexyldodecyldichlorosilane. The infrared spectrum of this compound is shown in FIG. 2. The absorption of Si--H band at 2213 cm-1 vanished. The NMR spectra of this compound is shown in FIG. 6. The formula (n--C6H13)(n--C12H25)SiCl2 for this compound was confirmed.
Reaction SMILES: [C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:12][CH2:11][C:10](=[O:13])[CH:9]=[CH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].[N:26](OC(C)(C)C)=[O:27].Cl>C(O)(C)(C)C.C(OCC)C>[C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:12][C:11](=[N:26][OH:27])[C:10](=[O:13])[CH:9]=[CH:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)ON=O
Reactant: O=C1C=CC(c2ccccc2)(c2ccccc2)CC1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: CCOCC
Product: O=C1C=CC(c2ccccc2)(c2ccccc2)CC1=NO
Temperature: 30 °C
Reaction time: 0.25 h

Procedure:
A solution of 10.1 g of 4,4-diphenylcyclohex-2-enone in 60 cm3 of tert-butanol is added to a solution of 6.5 g of potassium tert-butoxide in 50 cm3 of tert-butanol at a temperature in the region of 30° C. After stirring for about 15 minutes at a temperature in the region of 30° C., this solution is added dropwise to 14 cm3 of tert-butyl nitrite. The reaction mixture is stirred at a temperature in the region of 20° C. for 2 hours. 100 cm3 of aqueous 3 M hydrochloric acid solution and 100 cm3 of diethyl ether are then added to the preceding mixture at a temperature in the region of 20° C. After separation of the phases by settling, the aqueous phase is extracted with 100 cm3 of diethyl ether. The combined organic phases are washed with three times 100 cm3 of saturated aqueous sodium bicarbonate solution and then with 100 cm3 of saturated aqueous sodium chloride solution, and then dried over magnesium sulphate, filtered and concentrated. After concentrating to dryness under reduced pressure (13 kPa), the residue is purified by flash chromatography on a column of silica (eluent: cyclohexane/ethyl acetate (80/20 by volume)]. 2.23 g of 5,5-diphenylcyclohex-3-ene-1,2-dione 1-oxime are thus obtained in the form of a yellow foam, which is used without further modification for subsequent syntheses and the characteristics of which are as follows:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:17][CH2:16][CH2:15][C@H:14]3[N:9]2[C:10](=[O:19])[CH:11](I)[CH2:12][CH2:13]3)=[CH:4][CH:3]=1.[P:20]([O:27]CC)([O:24][CH2:25][CH3:26])[O:21][CH2:22][CH3:23]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:17][CH2:16][CH2:15][C@H:14]3[N:9]2[C:10](=[O:19])[CH:11]([P:20](=[O:27])([O:24][CH2:25][CH3:26])[O:21][CH2:22][CH3:23])[CH2:12][CH2:13]3)=[CH:4][CH:3]=1
Reactant: CCOP(OCC)OCC
Reactant: O=C1C(I)CC[C@H]2CCC[C@@H](c3ccc(Cl)cc3)N12
Product: CCOP(=O)(OCC)C1CC[C@H]2CCC[C@@H](c3ccc(Cl)cc3)N2C1=O
Temperature: 120 °C
Reaction time: 2 h

Procedure:
Iodotrimethylsilane (0.74 mL) was added to a solution of (6S,9aR)-6-(4-chlorophenyl)octahydroquinolizin-4-one (877 mg) and N,N,N′,N′-tetramethylethylenediamine (1.76 mL) in methylene chloride (25 mL) in a nitrogen atmosphere at 0° C., and the reaction solution was stirred at 0° C. for 30 minutes. Iodine (1.26 g) was added to the reaction solution at 0° C., and the reaction solution was stirred at 0° C. for one hour. A sodium thiosulfate solution and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over magnesium sulfate, and then concentrated under reduced pressure to obtain (6S,9aR)-6-(4-chlorophenyl)-3-iodooctahydroquinolizin-4-one. A mixture of (6S,9aR)-6-(4-chlorophenyl)-3-iodooctahydroquinolizin-4-one with triethyl phosphite (10 mL) was stirred at 120° C. for two hours. The reaction solution was left to cool to room temperature and concentrated under reduced pressure to obtain diethyl [(6S,9aR)-6-(4-chlorophenyl)-4-oxooctahydroquinolizin-3-yl]phosphonate. Lithium hydroxide monohydrate (422 mg) was added to a mixed solution of diethyl [(6S,9aR)-6-(4-chlorophenyl)-4-oxooctahydroquinolizin-3-yl]phosphonate and 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (869 mg) in tetrahydrofuran (21 mL) and ethanol (7 mL) at room temperature, and the reaction solution was stirred at room temperature for two hours. Ethyl acetate and saturated sodium bicarbonate water were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system) and then by silica gel column chromatography (elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain 1.07 g of the title compound. The property values of the compound are as follows.