Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH:2]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:24][CH:23]=1)[C:3]([N:5]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:6][CH:7]([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10])=[O:4].[CH2:33]([NH:40][C:41](=[O:51])[NH:42][C@H:43]([CH2:48][CH:49]=[CH2:50])[CH2:44][C:45](O)=[O:46])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[CH2:14]([N:5]([CH2:6][CH:7]([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10])[C:3]([CH:2]([NH:1][C:45](=[O:46])[CH2:44][CH:43]([NH:42][C:41]([NH:40][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:51])[CH2:48][CH:49]=[CH2:50])[CH2:21][C:22]1[CH:23]=[CH:24][C:25]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[CH:26][CH:27]=1)=[O:4])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: C=CC[C@H](CC(=O)O)NC(=O)NCc1ccccc1
Reactant: CCOC(CN(Cc1ccccc1)C(=O)C(N)Cc1ccc(OC(C)(C)C)cc1)OCC
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: C=CCC(CC(=O)NC(Cc1ccc(OC(C)(C)C)cc1)C(=O)N(Cc1ccccc1)CC(OCC)OCC)NC(=O)NCc1ccccc1
Reaction time: 0.67 h

Procedure:
To a solution of 2-Amino-N-benzyl-3-(4-tert-butoxy-phenyl)-N-(2,2-diethoxy-ethyl)-propionamide in CH2Cl2 (50 ml) was added a solution of (3R)-3-(3-Benzyl-ureido)-hex-5-enoic acid (1.6 g, 6.1 mmol), EDCI (1.17 g, 7.3 mmol, 1.2 eq), HOBt (0.93 g, 7.3 mmol, 1.2 eq), DIEA (2.13 mL, 12.2 mmol, 2.4 eq) in CH2Cl2 (100 mL) stirred for 40 min. The reaction mixture was stirred at room temperature for 14 h, and then diluted with EtOAc, washed with water and brine. The organic layer was dried with Na2SO4 and concentrated in vacuo. The crude compound was used next step without further purification. MS ESI 687 (M+H), 709 (M+Na)
Reaction SMILES: [OH-].[Na+].[OH:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1.[I-].[Na+].Cl[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][OH:21]>O.C(O)C>[OH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1
Reactant: OCCCCCCCl
Reactant: O=Cc1ccc(O)cc1
Agent: [I-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=Cc1ccc(OCCCCCCO)cc1
Yield: 90.9 %

Procedure:
To a solution of 40 g (1 mole) of sodium hydroxide in 60 ml of water and 400 ml of ethanol were added 122.12 g (1 mole) of 4-hydroxybenzaldehyde, 30 g of sodium iodide and 136.62 g (1 mole) of 1-chloro-6-hydroxyhexane. The mixture was heated at reflux for 24 hours under a nitrogen atmosphere. After cooling, the mixture was filtered and the solvent was removed under reduced pressure. Water (400 ml) was added to the residue and the mixture was extracted twice with 400 ml of ethyl acetate. The ethyl acetate layers were extracted twice with 200 ml of 5% aq. sodium hydroxide, and once with 200 ml of brine, dried over magnesium sulfate, and the solvent was evaporated. A brown oil (202 g, 91%) was obtained, which crystallized slowly.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH:16]([CH3:18])[CH3:17].O>CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH:16]([CH3:18])[CH3:17]
Reactant: CC(C)Br
Reactant: Oc1ccccc1Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)Oc1ccccc1Br
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.7 %

Procedure:
2-Bromophenol (500 mg, 2.9 mmol) was dissolved in dry dimethylformamide (5 mL) under a dry nitrogen atmosphere. Powdered dry cesium carbonate (1.41. g, 4.34 mmol) was added, followed by the addition of 2-bromopropane (404 μL, 4.05 mmol) over a 2 min period. The mixture was stirred at room temperature overnight. Water (50 mL) was added and the mixture extracted with ethyl acetate (2×50 mL). The combined extracts were successively washed with water (25 mL) and saturated salt solution (25 mL) and dried over anhydrous magnesium sulfate. The dried solution was filtered and the solvents removed rotoevaporation to yield the title compound as an oil (522 mg, 84% yield).
Reaction SMILES: [CH3:1][N:2]([CH3:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([OH:12])[CH:7]=1)=[S:4].C(OCC)(=O)C.[CH3:20][N:21]=[C:22]=[O:23]>CCCCCC>[CH3:1][N:2]([CH3:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:22](=[O:23])[NH:21][CH3:20])[CH:7]=1)=[S:4]
Reactant: CN=C=O
Reactant: CN(C)C(=S)Nc1cccc(O)c1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CNC(=O)Oc1cccc(NC(=S)N(C)C)c1
Temperature: 20 °C

Procedure:
1,1-dimethyl-3-(meta-methylcarbamoyloxyphenyl)-2-thiourea is prepared by charging to a suitable equipped reaction vessel about 32.7 parts by weight of 1,1-dimethyl-3-(meta-hydroxyphenyl)-2-thiourea, about 100 parts by weight of ethyl acetate, about 12 parts by weight of methyl isocyanate and about 1 part by weight triethylamino, refluxing for about 1 hour with stirring, diluting the resulting slurry with about 100 parts by weight of hexane, cooling to about 20°C., recovering the precipitate from the remainder by filtration, washing the recovered solid with ethyl acetate and hexane and air drying.
Reaction SMILES: [N+]([O-])([O-])=O.[Nd+3:5].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[C:14]([C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=1)([CH3:17])([CH3:16])[CH3:15].C(N(CC)CC)C>CO>[Nd:5].[C:14]([C:18]1[CH:19]=[CH:20][C:21]([C:22]([OH:24])=[O:23])=[CH:25][CH:26]=1)([CH3:17])([CH3:15])[CH3:16]
Reactant: [Nd+3]
Agent: CC(C)(C)c1ccc(C(=O)O)cc1
Agent: O=[N+]([O-])[O-]
Solvent: CO
Solvent: CCN(CC)CC
Product: [Nd]
Temperature: 30 °C

Procedure:
The compound was synthesized by the same method as that for Synthesis Example 1-2 above, that is, after forming a triethylamine salt of 4-tertiary-butylbenzoic acid in anhydrous methanol, a methanol solution of neodymium nitrate was added while stirring. Specifically, a reactor similar to that of 1-1 was used to stir a slurry solution obtained by adding 100 ml of an anhydrous methanol to 53.48 g (0.3 mol) of 4-tertiary-butylbenzoic acid, while dripping 30.4 g (0.3 mol) of triethylamine while maintaining at 30° C. by cooling in an ice water bath. After dripping, the solution was heated for 30 minutes at 40° C. to prepare a transparent synthesis solution of 4-tertiary-butylbenzoic acid-triethylamine salts. Next, 200 ml of methanol were further added to this synthesis solution and maintained at about 30° C., and a solution obtained by dissolving 43.8 g of neodymium nitrate into 100 ml of methanol was dripped in while stirring. Upon dripping of about half of the neodymium nitrate solution, it began to cloud, upon completion of dripping, a high-concentration slurry solution was obtained. After completion of dripping, the solution was heated to 40° C. for 30 minutes, to produce a slurry solution of a neodymium salt of 4-tertiary-butylbenzoic acid. Crystals obtained by filtering this slurry solution were added to 400 ml of methanol, stirred and washed, then refiltered, and 400 ml of methanol were once again added to the crystals stirred and washed, then filtered. The resulting crystals were dried under reduced pressure at 50° C., to obtain 59.3 g of a neodymium salt of 4-tertiary-butylbenzoic acid (yield 88%
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([I:11])[CH:10]=1)[C:5]([OH:7])=[O:6].Cl.CN(C)CCCC(N=C=N)C.[C:24](O)([CH3:27])([CH3:26])[CH3:25]>CN(C)C1C=CN=CC=1.ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([I:11])[CH:10]=1)[C:5]([O:7][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:6]
Reactant: O=C(O)c1cc(Br)cc(I)c1
Reactant: CC(C)(C)O
Agent: CC(CCCN(C)C)N=C=N
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CC(C)(C)OC(=O)c1cc(Br)cc(I)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 3-bromo-5-iodobenzoic acid (50 g, 153 mmol), 1-(3-dimethylaminopropyl)-ethylcarbodiimide hydrochloride (30.8 g, 153 mmol), 4-dimethylaminopyridine (18.6 g, 153 mmol) and t-butanol (69.4 g, 90 ml, 153 mmol) in dichloromethane (500 ml) was stirred at room temperature overnight. The reaction mixture was washed with 2MHCl and saturated NaHCO3. The organic phase was dried and evaporated to give the title compound as a light brown solid. (48 g; 85%).
Reaction SMILES: CC(C)([O-])C.[K+].C(OP([CH2:15][C:16]#[N:17])(=O)OCC)C.O=[C:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1>C1COCC1.O>[C:16]([CH:15]=[C:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)#[N:17]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: CCOP(=O)(CC#N)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(=CC#N)CC1
Temperature: 0 °C

Procedure:
To a three necked round bottom flask equipped with a mechanical stirring bar was added potassium tert-butoxide (263 mL, 263 mmol, 1.0 M in THF) and THF (200 mL). The mixture was cooled to 0° C., followed by the addition of diethyl(cyanomethyl)phosphonate (43.7 mL, 276 mmol) slowly by syringe. The reaction mixture was maintained at 0° C. for 10 minutes, then warmed to ambient temperature and maintained for 1 hour. The mixture was cooled to 0° C. and treated with the dropwise addition of tert-butyl 4-oxopiperidine-1-carboxylate (50.0 g, 251 mmol) in THF (150 mL) over 30 minutes. After addition, the mixture was maintained at 0° C. for 20 minutes, then warmed to ambient temperature and maintained for 18 hours. The reaction mixture was then diluted with water (800 mL) and extracted with EtOAc (700 mL×2). The combined organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford the title compound as a light pink solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11](=[O:13])[N:10]([CH3:14])[N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:17][Si:18]([CH3:25])([CH3:24])[CH2:19][CH2:20][O:21][CH2:22]Cl.CCOC(C)=O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]([CH2:22][O:21][CH2:20][CH2:19][Si:18]([CH3:25])([CH3:24])[CH3:17])[C:11](=[O:13])[N:10]([CH3:14])[N:9]=2)=[CH:6][CH:7]=1
Reactant: Cn1nc(-c2ccc(Br)cc2)[nH]c1=O
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cn1nc(-c2ccc(Br)cc2)n(COCC[Si](C)(C)C)c1=O
Reaction time: 0.33 h

Procedure:
To a solution of compound 51b (1.0 g, 3.9 mmol) in DMF (5 mL) was added sodium hydride (0.2 g, 5.0 mmol) in portions at 0° C. The mixture was stirred for 20 min, then 2-(trimethylsilyl)ethoxymethyl chloride (0.73 g, 4.4 mmol) was added dropwise. The reaction mixture was stirred at rt for 2 h. EtOAc (100 mL) was added. The organic layer was washed with water and brine, dried over Na2SO4, filtered and concentrated to give a residue, which was purified by flash column chromatography on silica gel (EtOAc/petroleum ether (1:5 v/v)) to afford compound 51c as a yellow solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C15H22BrN3O2Si: 384.1 (M+H). Found 384.1.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([NH:9][CH:10]=[O:11])=[C:4]([CH3:12])[C:3]=1[CH3:13].Br[CH2:15]/[CH:16]=[CH:17]/[C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1>C(OCC)(=O)C.CCCCCC>[F:24][C:21]1[CH:22]=[CH:23][C:18](/[CH:17]=[CH:16]/[CH2:15][O:1][C:2]2[CH:7]=[C:6]([CH3:8])[C:5]([NH:9][CH:10]=[O:11])=[C:4]([CH3:12])[C:3]=2[CH3:13])=[CH:19][CH:20]=1
Reactant: Fc1ccc(/C=C/CBr)cc1
Reactant: Cc1cc(O)c(C)c(C)c1NC=O
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: Cc1cc(OC/C=C/c2ccc(F)cc2)c(C)c(C)c1NC=O
Yield: 52 %

Procedure:
By using N-(4-hydroxy-2,3,6-trimethylphenyl)formamide and 1-[(E)-3-bromo-1-propenyl]-4-fluorobenzene, the title compound was synthesized according to Reference Example 17b. Yield: 52%. Melting point: 196-198° C. (Ethyl acetate-hexane).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1>CO>[Cl-:1].[CH2:2]1[N+:5]2([CH2:9][CH2:8][CH2:7][CH2:6]2)[CH2:4][CH2:3]1
Reactant: ClCCCN1CCCC1
Solvent: CO
Product: C1CC[N+]2(C1)CCC2
Product: [Cl-]

Procedure:
1-(3-Chloropropyl)pyrrolidine (1.142 g) was dissolved in methanol (38 ml) and the solution refluxed overnight. The solution was evaporated to dryness on a rotary evaporator to give 4-azoniaspiro[3,4]octane chloride as an impure oil.
Reaction SMILES: [NH2:1][CH2:2][C:3]([OH:5])=[O:4].F[C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][CH:8]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O>[N+:13]([C:10]1[CH:11]=[CH:12][C:7]([NH:1][CH2:2][C:3]([OH:5])=[O:4])=[CH:8][CH:9]=1)([O-:15])=[O:14]
Reactant: NCC(=O)O
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)CNc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 72 %

Procedure:
Glycine (5.31 g, 70.8 mmol) was added to a mixture of 1-fluoro-4-nitro-benzene (5.0 g, 35.4 mmol) and sodium bicarbonate (5.94 g, 70.8 mmol) in dioxane (10 mL) and water (60 mL) and heated at reflux for 6 h. The reaction mixture was cooled to room temperature and washed with ethyl acetate. The aqueous layer was acidified with 1N hydrochloric acid to pH ˜3 and extracted with ethyl acetate. The extract was washed with water, brine, dried over anhydrous sodium sulfate and concentrated to dryness to afford (4-nitro-phenylamino)-acetic acid (5.0 g, 72%) as a yellow solid.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[P:6]([O:11][CH2:12][CH3:13])(=[O:10])[O:7][CH2:8][CH3:9].C([N-]C(C)C)(C)C.[Li+].[CH2:22]([Sn:26](Cl)([CH2:31][CH2:32][CH2:33][CH3:34])[CH2:27][CH2:28][CH2:29][CH3:30])[CH2:23][CH2:24][CH3:25]>C1COCC1>[CH2:31]([Sn:26]([CH2:22][CH2:23][CH2:24][CH3:25])([CH2:27][CH2:28][CH2:29][CH3:30])[C:5]1[O:1][C:2]([P:6]([O:7][CH2:8][CH3:9])(=[O:10])[O:11][CH2:12][CH3:13])=[CH:3][CH:4]=1)[CH2:32][CH2:33][CH3:34]
Reactant: CCOP(=O)(OCC)c1ccco1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1ccc(P(=O)(OCC)OCC)o1
Temperature: -78 °C
Reaction time: 0.33 h

Procedure:
A solution of diethyl 2-furanphosphonate (1 mmol) in 2 mL THF was cooled to −78° C. and added to a solution of lithium diisopropylamide (LDA) (1 mmol) in 5 mL THF at −78° C. over 20 min. The resulting mixture was stirred −78° C. for 20 min and added into a solution of tributyltin chloride (1 mmole) in 1 mL THF at −78° C. over 20 min. The mixture was then stirred at −78° C. for 15 min, and at 25° C. for 1 h. Extraction and chromatography gave diethyl 5-tributylstannyl-2-furanphosphonate as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][C:3]=1[N+:13]([O-])=O>CC(O)C.O.Cl.C(OCC)C.[Fe]>[NH2:13][C:3]1[CH:4]=[C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:7][C:2]=1[F:1]
Reactant: COC(=O)Cc1ccc(F)c([N+](=O)[O-])c1
Agent: [Fe]
Agent: Cl
Solvent: CCOCC
Solvent: O
Solvent: CC(C)O
Product: COC(=O)Cc1ccc(F)c(N)c1
Reaction time: 2 h
Yield: 83.1 %

Procedure:
Methyl 4-fluoro-3-nitrophenylacetate (5.0 g, 0.023 mol) and iron powder (3 g, 0.053 mol) were suspended in a mixture of propan-2-ol (50 ml) and water (5 ml). Concentrated hydrochloric acid (5 drops) was added at room temperature and the mixture was heated at reflux with stirring for 2 hours. The reaction mixture was cooled, diluted with diethyl ether, filtered through diatomaceous earth and the resulting filtrate was evaporated in vacuo. The residue was further purified by chromatography on silica gel, eluting with diethyl ether to yield methyl 3-amino-4-fluorophenylacetate (3.5 g) as a yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[C:30]4[C@H:37]([CH3:38])[CH2:36][C@@H:35]([OH:39])[C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:25][CH2:24]2)=[O:22])[CH2:9][N:10]([CH:18]([CH3:20])[CH3:19])C(=O)OC(C)(C)C)=[CH:4][CH:3]=1.Cl.CCOCC>O1CCOCC1.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([CH2:9][NH:10][CH:18]([CH3:20])[CH3:19])[C:21]([N:23]2[CH2:24][CH2:25][N:26]([C:29]3[C:30]4[C@H:37]([CH3:38])[CH2:36][C@@H:35]([OH:39])[C:31]=4[N:32]=[CH:33][N:34]=3)[CH2:27][CH2:28]2)=[O:22])=[CH:4][CH:3]=1
Reactant: CC(C)N(C[C@@H](C(=O)N1CCN(c2ncnc3c2[C@H](C)C[C@H]3O)CC1)c1ccc(Cl)cc1)C(=O)OC(C)(C)C
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Solvent: CCOCC
Product: CC(C)NC[C@@H](C(=O)N1CCN(c2ncnc3c2[C@H](C)C[C@H]3O)CC1)c1ccc(Cl)cc1
Reaction time: 8 h

Procedure:
The tert-butyl (S)-2-(4-chlorophenyl)-3-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (2.50 g, 4.48 mmol) was dissolved in dioxane (22.4 mL) and treated with 4M HCl in dioxane (22.4 mL, 89.6 mmol) at room temperature. The resulting solution was allowed to stir overnight to completion by LCMS analysis of the crude. The solution was concentrated in vacuo to afford a gel that was dissolved in a minimal amount of methanol (10 mL). The solution was transferred via pipette to stirred ether (300 mL) to afford a white precipitate of desired product. The addition was about half when the white precipitate melted into a yellow gel. The material was concentrated in vacuo to afford a yellow gel which was allowed to stand under reduced pressure overnight to yield (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propan-1-one dihydrochloride as a light yellow powder (2.14 g, 90%).
Reaction SMILES: [S:1]1[C:5]2[S:6][CH2:7][CH2:8][C:9](=[O:10])[C:4]=2[CH:3]=[CH:2]1.[CH2:11]=O.[ClH:13].[CH3:14][NH:15][CH3:16]>C(O)(=O)C>[ClH:13].[CH3:14][N:15]([CH2:11][CH:8]1[CH2:7][S:6][C:5]2[S:1][CH:2]=[CH:3][C:4]=2[C:9]1=[O:10])[CH3:16]
Reactant: C=O
Reactant: CNC
Reactant: O=C1CCSc2sccc21
Agent: Cl
Solvent: CC(=O)O
Product: CN(C)CC1CSc2sccc2C1=O
Temperature: 100 °C
Reaction time: 1 h
Yield: 83.5 %

Procedure:
A mixture of 5,6-dihydrothieno[2,3-b]thiopyran-4-one (12.5 g, 0.074 mol), paraformaldehyde (7.5 g, 0.25 mol), dimethylamine-hydrochloride (40 g, 0.49 mol) and acetic acid (2 ml) was heated with stirring at 100° C. for 1 hour. After allowing to cool to room temperature, the solid was triturated with ethanol and the solid was collected on a filter to yield 16.3 g (83%) of the title compound. An analytical sample was prepared by crystallization from 95% ethanol and filtration through a pad of norite-ducco-supercel to yield product with mp 155°-157° C. Anal. Calc'd. for C10H13NOS2.HCl.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11](OS(C(F)(F)F)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:30]2[CH:35]=[CH:34][C:33]([NH2:36])=[CH:32][CH:31]=2)O1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>C1(C)C=CC=CC=1.C(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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:30]2[CH:35]=[CH:34][C:33]([NH2:36])=[CH:32][CH:31]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC1(C)OB(c2ccc(N)cc2)OC1(C)C
Reactant: CC(C)(C)OC(=O)N1CC=C(OS(=O)(=O)C(F)(F)F)CC1
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: [Na+]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CC=C(c2ccc(N)cc2)CC1
Temperature: 80 °C
Reaction time: 3 h
Yield: 64.8 %

Procedure:
To a mixture of 4-trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (Synthesis, 993, (1991), 7.4 g, 22 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (4.0 g, 18 mmol) and Pd(PPh3)4 (2.3 g, 2.0 mmol) in 160 mL of toluene and 80 mL of absolute ethanol under Ar was added 2.0 M aq Na2CO3 solution (80 mL, 160 mmol). The resulting mixture was stirred at 80° C. for 3 h and then cooled to RT. After adding 600 mL of EtOAc, the mixture was washed with 1 M NaOH (250 mL), H2O (2×250 mL), brine (300 mL) and dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (20% EtOAc/hexane) gave 3.20 g (63%) of the title compound as a hard yellow foam: Mass spectrum (ESI, m/z): Calcd. for C16H22N2O2, 275.2 (M+H), found 275.1.
Reaction SMILES: [CH3:1][Si:2]([CH3:15])([CH3:14])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[CH:11]=[C:10]([C:12]#[N:13])[N:9]=[CH:8]1.[Br:16]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C(Cl)(Cl)(Cl)Cl.CCOC(C)=O>[Br:16][C:8]1[N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:15])([CH3:14])[CH3:1])[CH:11]=[C:10]([C:12]#[N:13])[N:9]=1
Reactant: C[Si](C)(C)CCOCn1cnc(C#N)c1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Product: C[Si](C)(C)CCOCn1cc(C#N)nc1Br
Temperature: 60 °C
Yield: 77.9 %

Procedure:
To a solution of 1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-4-carbonitrile (0.70 g, 3.1 mmol) (as prepared in the previous step) in CCl4 (10 mL) was added N-bromosuccinimide (NBS) (0.61 g, 3.4 mmol) and azobis(isobutyronitrile) (AIBN, catalytic), and the mixture was heated at 60° C. for 4 h. The reaction was diluted with EtOAc (30 mL), washed with NaHCO3 (2×30 mL), brine (30 mL), the organic layer was dried over Na2SO4 and then concentrated. The title compound was eluted from a 20-g SPE cartridge (silica) with 30% EtOAc/hexane to give 0.73 g (77%) of a yellow solid: Mass spectrum (CI (CH4), m/z) Calcd. for C10H16BrN3OSi, 302.0/304.0 (M+H). found 302.1/304.1.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl.[CH3:15]O>>[F:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([O:6][CH3:15])=[O:5]
Reactant: CO
Reactant: O=C(O)c1cc([N+](=O)[O-])ccc1F
Agent: Cl
Product: COC(=O)c1cc([N+](=O)[O-])ccc1F
Temperature: 70 °C

Procedure:
To a solution of 2-fluoro-5-nitrobenzoic acid (5 g, 27.0 mmol) in methanol (135 mL) was added HCl (2.66 mL, 32.4 mmol, 12.2 M), and the mixture was heated with an oil bath at 70° C. for 24 hours. The solvent was evaporated, and the residue was dissolved in ethyl acetate and washed with saturated sodium bicarbonate and brine, dried over sodium sulfate, and concentrated to afford the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.63 (dd, J=3.0, 6.2, 1H), 8.58-8.50 (m, 1H), 7.74-7.61 (m, 1H), 3.92 (s, 3H).
Reaction SMILES: C1C2NC3C(=CC=CC=3)SC=2C=CC=1.P(=O)(O)(O)O.[CH2:20]=[CH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.ClC1C=CC=CC=1C=C.Cl[CH2:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>>[CH3:38][CH:39]1[C:40]2[C:45](=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:20]1
Reactant: ClCCc1ccccc1
Reactant: C=Cc1ccccc1
Agent: C=Cc1ccccc1Cl
Agent: O=P(O)(O)O
Agent: c1ccc2c(c1)Nc1ccccc1S2
Product: CC1CC(c2ccccc2)c2ccccc21
Temperature: 38 °C

Procedure:
1 part of phenothiazine is added to 375 parts by volume of phosphoric acid (95% strength by weight) at 25° C, in a stirred vessel. The mixture is irradiated for 10 minutes with a mercury vapor lamp (15 watt hours per kilogram of styrene II and III) whilst passing 2,000 parts of air through it. A mixture of 52 parts of styrene, 78 parts of o-chlorostyrene and 42 parts of o-chloroethylbenzene is then added to the irradiated solution over 3 hours at a temperature of 38° C. After completion of the addition, the mixture is stirred for a further hour at 38° C. The organic phase is separated off, washed with 200 parts of 5 per cent strength by weight sodium hydroxide solution and fractionated. 13.8 parts of 1-methyl-3-phenylindan (b.p. 145° to 146° C (10 mm)), 85 parts of 1-methyl-3-(o-chloro)-phenylindan (b.p. 165° to 168° C (10 mm), nD25 : 1.5890) and 5 parts of 1-methyl-3-(o-chloro)-phenyl-7-chloroindan (b.p. 195° to 200° C (10 mm)) are isolated.