Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: OC1C=CC(C2C=CN=C(NC3C=C(OC)C(OC)=C(OC)C=3)N=2)=CC=1.C([O:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41][C:42]2[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49]3[CH:54]=[C:53]([O:55][CH3:56])[C:52]([O:57][CH3:58])=[C:51]([O:59][CH3:60])[CH:50]=3)[N:43]=2)=[CH:37][CH:36]=1)C1C=CC=CC=1.C([O-])=O.[NH4+]>[Pd]>[OH:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41][C:42]2[CH:47]=[CH:46][N:45]=[C:44]([NH:48][C:49]3[CH:54]=[C:53]([O:55][CH3:56])[C:52]([O:57][CH3:58])=[C:51]([O:59][CH3:60])[CH:50]=3)[N:43]=2)=[CH:37][CH:36]=1
Reactant: COc1cc(Nc2nccc(Nc3ccc(OCc4ccccc4)cc3)n2)cc(OC)c1OC
Agent: [Pd]
Agent: COc1cc(Nc2nccc(-c3ccc(O)cc3)n2)cc(OC)c1OC
Agent: O=C[O-]
Product: COc1cc(Nc2nccc(Nc3ccc(O)cc3)n2)cc(OC)c1OC
Yield: 99.5 %

Procedure:
In a manner analogous to the preparation of the compound of Example 49 from the compound of Example 104 (3.0 g, 6.55 mmol), ammonium formate (1.20 g, 19.60 mmol) and 10% palladium on carbon (300 mg) to give the title compound (2.40 g) as a white solid m.p. 112-115°. δH (CDCl3) 7/96)1H. d, J 5.9 Hz), 7.16 (2H, d, J 8.7 Hz), 7.06 (1H, s), 6.83 (1H, s), 6.80 (3H, m), 6.68 (1H, s), 6.01 (1H, d, J 5.9 Hz), 3.79 (3H, s) and 3.78 (6H, s). MS m/z 369 (M+H)+.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:15]([NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)#[N:16]>CC(C)=O>[CH2:7]([N:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]1=[N:17][C:15]#[N:16])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: N#CNc1ccccn1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: N#CN=c1ccccn1Cc1ccccc1
Reaction time: 2.5 h
Yield: 53 %

Procedure:
7 g (50 mmole) of potassium carbonate and 6.5 ml (55 mmole) of benzyl bromide are weighted to the suspension of 6 g (50 mmole) of 2-(cyanoamino)pyridine in 100 ml of acetone, then the reaction mixture is refluxed under vigorous stirring for 2.5 hours. After cooling the inorganic salt is filtered off and the acetone filtrate is evaporated under reduced pressure. The residue is triturated with 10 ml of ether, filtered and washed twice with 5 ml of ether each to obtain 5.55 g (53.1%) of the named compound, m.p.: 142° C.
Reaction SMILES: O[CH2:2][CH2:3][C:4]1[N:9]2[CH:10]=[CH:11][N:12]=[C:8]2[CH:7]=[CH:6][CH:5]=1.S(Cl)(Cl)=O.[Na].[S:18]1[CH2:22][C:21](=[O:23])[NH:20][C:19]1=[O:24].[I-].[Na+]>C(Cl)(Cl)Cl.CN(C)C=O.O>[N:12]1[CH:11]=[CH:10][N:9]2[C:4]([CH2:3][CH2:2][N:20]3[C:21](=[O:23])[CH2:22][S:18][C:19]3=[O:24])=[CH:5][CH:6]=[CH:7][C:8]=12
Reactant: O=C1CSC(=O)N1
Reactant: OCCc1cccc2nccn12
Agent: [I-]
Agent: [Na+]
Agent: [Na]
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: O=C1CSC(=O)N1CCc1cccc2nccn12
Temperature: 80 °C
Reaction time: 16 h

Procedure:
To a suspension of 4.0 g (24.7 mmol) of 5-(2-hydroxyethyl)imidazo[1,2-a]pyridine in 30 ml of chloroform, 5 ml (68 mmol) of thionyl chloride was added. After refluxing for 2 hours, the solvent was distilled off. To a suspension of the residue and 8.36 g (60 mmol) of 2,4-thiazolidinedione sodium salt in 50 ml of N,N-dimethylformamide, 3.75 g (25 mmol) of sodium iodide was added, followed by stirring at 80° C. for 16 hours. After the reaction mixture was cooled, water was added. The reaction mixture was then extracted with ethyl acetate and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent: n-hexane/ethyl acetate=2/1→1/1→1/4) to yield 1.00 g (15.5%, light orange powder) of the desired product.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:8]=[O:9].OO>[O-][W]([O-])(=O)=O.[Na+].[Na+].O>[CH:8]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:9]
Reactant: C=O
Reactant: Nc1ccccc1
Agent: O=[W](=O)([O-])[O-]
Agent: OO
Agent: [Na+]
Solvent: O
Product: O=CNc1ccccc1

Procedure:
18.6 g (0.2 mol) of aniline are introduced into 30 ml of water, followed by the dropwise addition with stirring of 20 g (0.2 mol) of a 30 % by weight aqueous formaldehyde solution. 0.2 g of sodium tungstate are then added, followed by the dropwise addition with continued stirring of 25 g of a 30 % by weight aqueous hydrogen peroxide solution. The temperature rises to about 60° to 70°C. The dark oil precipitated is taken up in about 30 ml of methylene chloride and the organic phase is separated off. The aqueous phase is repeatedly extracted with methylene chloride. The combined organic phases are dried over sodium sulphate and subsequently subjected to fractional distillation in vacuo, giving 12.2 g (51 % of the theoretical yield) of formanilide boiling at 160° to 172°C/ 15 Torr.
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][C:14]=2[F:20])[CH:10]=[N:9]1)([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:30]2[CH:31]=[N:32][C:33]([NH2:36])=[N:34][CH:35]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[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>[NH2:36][C:33]1[N:34]=[CH:35][C:30]([C:16]2[CH:17]=[CH:18][C:13]([C:11]3[CH:10]=[N:9][N:8]([CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:21])[CH:12]=3)=[C:14]([F:20])[CH:15]=2)=[CH:31][N:32]=1
Reactant: CC1(C)OB(c2cnc(N)nc2)OC1(C)C
Reactant: CC(C)(C)OC(=O)Cn1cc(-c2ccc(Br)cc2F)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)Cn1cc(-c2ccc(-c3cnc(N)nc3)cc2F)cn1
Temperature: 120 °C

Procedure:
To a solution of tert-butyl[4-(4-bromo-2-fluorophenyl)-1H-pyrazol-1-yl]acetate (400 mg, 0.001 mol) in 1,4-dioxane (3 mL) was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (270 mg, 1.2 mmol), potassium phosphate (640 mg, 3.0 mmol) and tetrakis(triphenylphosphine)palladium (70 mg, 0.06 mmol). The solution was degassed with N2, and heated at 120° C. for 3 h. The solution was cooled to RT, poured into water, extracted with EtOAc, washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatograph on a silica gel column with EtOAc in Hexanes (50%) to afford the desired compound. LCMS: (M+H)=370.1.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[CH:10][C:11]([C:14]([OH:16])=O)=[N:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(Cl)Cl.C(Cl)(=O)OCC.[CH2:27]([NH2:29])[CH3:28]>O.C(N(CC)CC)C>[CH2:27]([NH:29][C:14](=[O:16])[C:11]1[CH:10]=[CH:9][C:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:13][N:12]=1)[CH3:28]
Reactant: O=C(O)c1ccc(Cc2ccccc2)cn1
Reactant: CCN
Agent: CCOC(=O)Cl
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: CCN(CC)CC
Product: CCNC(=O)c1ccc(Cc2ccccc2)cn1
Reaction time: 0.5 h

Procedure:
2.1 Grams of 5-benzylpicolinic acid were dissolved in 20 ml. of chloroform. The resulting solution was then added with 1.2 g of triethylamine and 1.1 g of ethyl chlorocarbonate and thereafter with 33% ethylamine solution dropwise under ice-cooling and stirring. After 30 minutes 10 ml. of water were added thereto and the mixture was fractionated. The organic layer was washed with 10% aqueous ammonia. After drying, the solvent was distilled out. The residue was recrystallized from n-hexane to obtain 2.0 g of 5-benzyl-picolinic acid N-ethylamide as colorless crystals of a melting point of 77°~78° C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11]O)([O-:3])=[O:2].P(Br)(Br)[Br:14].O>C1C=CC=CC=1>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][Br:14])([O-:3])=[O:2]
Reactant: BrP(Br)Br
Reactant: O=[N+]([O-])c1ccccc1CCO
Solvent: c1ccccc1
Solvent: O
Product: O=[N+]([O-])c1ccccc1CCBr

Procedure:
2.5 ml of 2-(2-nitrophenyl)ethanol and 5.4 ml of PBr3 were stirred and mixed at 0° C. for 30 minutes to carry out reaction, and the resultant reaction mixture was diluted with 30 ml of benzene and the diluted mixture was then poured into 30 ml of water. The separated organic layer was separated, dried over anhydrous sodium sulfate, and then treated under reduced pressure to distill off the solvent, thereby obtaining 3 g of the crude product of 2-(2-nitrophenyl)ethyl bromide.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[N:6][CH:7]=1.ClC1C=C(C=CC=1)C(OO)=[O:17].[OH-].[Ca+2].[OH-]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:11])([CH3:9])[CH3:10])=[N+:6]([O-:17])[CH:7]=1
Reactant: CC(C)(O)c1ccc(Br)cn1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: [Ca+2]
Agent: [OH-]
Solvent: ClCCl
Product: CC(C)(O)c1ccc(Br)c[n+]1[O-]
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 5-bromo-2-(1-hydroxy-1-methylethyl)pyridine from Step 1 in methylene chloride (5 ml/mmol) at room temperature was added m-chloroperoxybenzoic acid 70% (1.1 eq) and the resulting mixture was stirred at room temperature for 18 hours. An excess of calcium hydroxide was added and after 5 minutes the mixture was filtered through a bed of celite. The crude product from evaporation of the filtrate was chromatographed on silica gel eluting with 80% ethyl acetate in hexane and the 5-bromo-2-(1-hydroxy-1-methylethyl)pyridine N-oxide compound was obtained as a white solid.
Reaction SMILES: C(O[C@:5]1([C:24]#[CH:25])[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:20]([CH2:21][CH2:22][C@:6]12[CH3:7])[C@@H:19]1[C:14](=[CH:15][C:16](=[O:23])[CH2:17][CH2:18]1)[CH2:13][CH2:12]3)(=O)C.C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1>>[C:24]([C:5]1[C@:6]2([CH2:22][CH2:21][C@H:20]3[C@@H:11]([CH2:12][CH2:13][C:14]4[C@@H:19]3[CH2:18][CH2:17][C:16](=[O:23])[CH:15]=4)[C@@H:8]2[CH2:9][CH:10]=1)[CH3:7])#[CH:25]
Reactant: C#C[C@@]1(OC(C)=O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@@]21C
Solvent: c1ccc(-c2ccccc2)cc1
Solvent: c1ccc(Oc2ccccc2)cc1
Product: C#CC1=CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]12C
Yield: 60.7 %

Procedure:
One gram of 17α-acetoxy-17β-ethynyl-4-estren-3-one is treated analogously to Example 1 in "Dowtherm" for 10 minutes at 250° C. and worked up. Recrystallization from isopropyl ether yields 500 mg of 17-ethynyl-4,16-estradien-3-one, m.p. 148°-152° C. (40% of theory).
Reaction SMILES: [Li]CCCC.Br[C:7]1[S:11][CH:10]=[N:9][CH:8]=1.[Sn:12](Cl)([CH2:21][CH2:22][CH2:23][CH3:24])([CH2:17][CH2:18][CH2:19][CH3:20])[CH2:13][CH2:14][CH2:15][CH3:16].Cl>C1COCC1.CCCCCC>[CH2:21]([Sn:12]([CH2:13][CH2:14][CH2:15][CH3:16])([CH2:17][CH2:18][CH2:19][CH3:20])[C:7]1[S:11][CH:10]=[N:9][CH:8]=1)[CH2:22][CH2:23][CH3:24]
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: Brc1cncs1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCC[Sn](CCCC)(CCCC)c1cncs1
Temperature: 25 °C
Reaction time: 1 h
Yield: 34.7 %

Procedure:
A hexane solution of n-BuLi (4.14 mL, 10 mmol) was added dropwise to an anhydrous tetrahydrofuran solution of 5-bromothiazole (0.46 mL, 5.0 mmol) at −78° C. under nitrogen atmosphere over a period of 30 minutes, and the mixture was stirred for 1 hour. A solution of n-Bu3SnCl (1.41 mL, 5.0 mmol) in THF was then added dropwise over a period of 30 minutes at −78° C., and after stirring for 2 hours, the mixture was raised to room temperature and stirred for another hour. Three drops of a 1N HCl solution were added, and the organic layer was extracted from the aqueous layer twice with 10 mL of ether. The solvent was distilled away to yield the title compound (650 mg, 35 mL)
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].[F:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][C:25]=1[C:33]([F:36])([F:35])[F:34].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:28](=[O:29])[C:27]3[CH:31]=[CH:32][C:24]([F:23])=[C:25]([C:33]([F:36])([F:34])[F:35])[CH:26]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1
Reactant: NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Reactant: O=C(Cl)c1ccc(F)c(C(F)(F)F)c1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C1CCC(N2C(=O)c3cccc(CNC(=O)c4ccc(F)c(C(F)(F)F)c4)c3C2=O)C(=O)N1
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.2 %

Procedure:
To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) and 4-fluoro-3-trifluoromethyl-benzoyl chloride (0.6 g, 2.8 mmol) in dry methylene chloride (60 mL), was added diisopropylethylamine (0.7 g, 5.4 mmol). After stirring at room temperature overnight, the reaction mixture was quenched with methanol (1 mL). The resulting suspension was filtered, and the solid was washed with methyene chloride to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-fluoro-3-trifluoromethyl-benzamide (0.8 g, 79%) as a white solid: mp 171-173° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=7.5 min. (99%); 1H NMR (DMSO-d6) δ 2.06-2.12 (m, 1H), 2.54-2.65 (m, 2H), 2.85-2.98 (m, 1H), 4.97 (d, J=5.7 Hz, 2H), 5.15-5.21 (dd, J=5.4 and 12.5 Hz, 1H), 7.68 (t, J=8.9 Hz, 1H), 7.76-7.84 (m, 3H), 8.28-8.35 (m, 2H), 9.43 (t, J=5.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 21.91, 30.86, 38.43, 48.82, 116.20 (116.37, 116.64, 116.80), 117.35 (117.63), 120.50 (124.10), 121.92, 126.51 (126.56), 127.14, 130.65 (130.70), 131.48, 133.22, 134.58, 134.71 (134.77), 138.70, 158.78 (162.21), 164.19, 166.87, 167.44, 169.75, 172.68; Anal. Calcd. for C22H15N3O5F4+0.2H2O: C, 54.94; H, 3.23; N, 8.74; F, 15.80. Found: C, 54.68; H, 3.17; N, 8.63; F, 15.72.
Reaction SMILES: CCCCCC.I[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1>COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH:16]1[C:17]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:13]=[CH:14][CH:15]=1
Reactant: Ic1cccc2ccccc12
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCCCCC
Solvent: COCCOC
Product: c1ccc2ccccc2c1
Yield: 30 %

Procedure:
Following General Procedure I, a mixture of hexane washed KH (160 mg, 4.0 mmol, 2.0 equiv), (Z)-21 (344 mg, 2.0 mmol, 1.0 equiv), 1-iodonaphthalene (292 μL, 2.0 mmol) and Pd(dba)2 (58 mg, 0.1 mmol, 0.05 equiv) was stirred in DME (4 mL) at room temperature for 15 min, and then was filtered through SiO2. Purification by column chromatography (RP C18, MeOH/H2O, 9/1) afforded 219 mg (49%) of (Z)-152a and 77 mg (30%) of naphthalene.
Reaction SMILES: [CH3:1][C:2]1[C:7]2[O:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[Br:21]Br>CCCCCC>[Br:21][C:3]1[CH:4]=[CH:5][C:6]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[O:8][C:7]=2[C:2]=1[CH3:1]
Reactant: BrBr
Reactant: Cc1cccc2c1oc1ccccc12
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCCCCC
Product: Cc1c(Br)ccc2c1oc1ccccc12
Temperature: 25 °C
Reaction time: 72 h

Procedure:
4-Methyldibenzofuran (30 g, 165 mmol) and sodium carbonate (17.5 g, 165 mmol) were mixed in hexane (300 ml) and bromine (26.4 g, 165 mmol) was added. The reaction was stirred at room temperature for 72 hours, then the solvent was removed in vacuo to give an oil which crystallised. Recrystallisation from IMS yielded several batches of off-white crystals (31.22 g, 72%) with m.p. 124°-125° C. (Found: C, 58.59; H, 3,28. C13H9BrO 0.31H2O requires: C, 58.58; H, 3.63%); δH [2H6 ]-DMSO 8.15 (1H, d), 7.9 (1H, d), 7.7 (1H, d), 7.4 (1H, t), 7.05 (2H, m), 2.6 (3H, s); m/z 260/262 (M+).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([Cl:10])[CH:7]=[C:6]([OH:11])[C:3]=1[CH:4]=[O:5].Cl(O)(=O)(=O)=O.OO.[CH3:19][OH:20]>[O-2].[V+5].[O-2].[O-2].[O-2].[O-2].[V+5]>[Cl:1][C:2]1[CH:9]=[C:8]([Cl:10])[CH:7]=[C:6]([OH:11])[C:3]=1[C:4]([O:20][CH3:19])=[O:5]
Reactant: CO
Reactant: O=Cc1c(O)cc(Cl)cc1Cl
Agent: [V+5]
Agent: OO
Agent: [O-2]
Product: COC(=O)c1c(O)cc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A solution of 2,4-dichloro-6-hydroxybenzaldehyde (5.00 g, 26.18 mmol) in 125 mL methanol was cooled to 0° C. Perchloric acid (70%, 1.47 mL, 16.23 mmol) was added, and the solution was stirred for 10 minutes. To a separate flask, vanadium (V) oxide (0.190 g, 1.05 mmol) was added to a hydrogen peroxide solution (30% in H2O, 11.90 mL, 104.7 mmol) at 0° C. This solution was stirred until the catalyst was dissolved, resulting in a clear orange solution, which was added dropwise to the methanol solution. The reaction was allowed to slowly warm to room temperature and stir overnight. The solution was concentrated under vacuum, and the residue dissolved in ethyl acetate. The organic extract was washed with aqueous sodium bicarbonate and brine, dried over Na2SO4, filtered and concentrated. The residue was filtered through a silica gel plug with 10% ethyl acetate in hexanes to provide methyl 2,4-dichloro-6-hydroxybenzoate that gave proton NMR spectra consistent with theory.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][CH2:20][OH:21])=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl.O>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][CH2:19][CH:20]=[O:21])=[CH:16][CH:17]=1
Reactant: OCCCc1ccc(Cl)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: O=CCCc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 48.6 %

Procedure:
To a stirred solution of oxalyl chloride (2.04 ml) in dichloromethane (40 ml) at −78° C. was added dimethyl sulphoxide (3.33 ml), and the reaction stirred for 10 min. 3-(4-Chlorophenyl)propanol (2.0 g) in dichloromethane (20 ml) was added and the reaction stirred at −78° C. for 75 min. Triethylamine (11.53 ml) was added, the reaction allowed to warm to room temperature, and stirred for 30 min. Water (150 ml) was added, and the reaction extracted with dichloromethane (2×100 ml). The combined organic extracts were washed with water (3×100 ml), dried over magnesium sulphate (2 g), and the solvent removed in vacuo to yield a yellow oil. This was purified by flash chromatography (silica, eluent dichloromethane) to yield the title compound as a pale yellow oil (0.96 g).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([CH3:31])([C:27]([F:30])([F:29])[F:28])[C:23]([F:26])([F:25])[F:24])[CH:19]=[CH:18][C:17]=2[O:32][CH3:33])[C@@H:9]1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=O)(C)(C)C.[ClH:40].Cl.CC(C1C=CC(OC)=C(C=1)CN[C@H]1CCCN[C@H]1C1C=CC=CC=1)(C)C#CC(F)(F)F>>[ClH:40].[ClH:40].[C:34]1([C@H:9]2[C@@H:10]([NH:14][CH2:15][C:16]3[CH:21]=[C:20]([C:22]([CH3:31])([C:27]([F:28])([F:29])[F:30])[C:23]([F:24])([F:25])[F:26])[CH:19]=[CH:18][C:17]=3[O:32][CH3:33])[CH2:11][CH2:12][CH2:13][NH:8]2)[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: COc1ccc(C(C)(C(F)(F)F)C(F)(F)F)cc1CN[C@H]1CCCN(C(=O)OC(C)(C)C)[C@H]1c1ccccc1
Agent: COc1ccc(C(C)(C)C#CC(F)(F)F)cc1CN[C@H]1CCCN[C@H]1c1ccccc1
Agent: Cl
Product: COc1ccc(C(C)(C(F)(F)F)C(F)(F)F)cc1CN[C@H]1CCCN[C@H]1c1ccccc1

Procedure:
This compound was prepared from Compound 77 in the same manner of Compound 60.
Reaction SMILES: [CH2:1]([NH2:3])[CH3:2].Cl[SiH:5]1[N:9]([CH:10]([CH2:12][CH3:13])[CH3:11])[CH:8]=[CH:7][N:6]1[CH:14]([CH2:16][CH3:17])[CH3:15]>CCCCCC>[CH:14]([N:6]1[CH:7]=[CH:8][N:9]([CH:10]([CH2:12][CH3:13])[CH3:11])[SiH:5]1[NH:3][CH2:1][CH3:2])([CH2:16][CH3:17])[CH3:15]
Reactant: CCC(C)N1C=CN(C(C)CC)[SiH]1Cl
Reactant: CCN
Solvent: CCCCCC
Product: CCN[SiH]1N(C(C)CC)C=CN1C(C)CC
Temperature: 25 °C
Reaction time: 2 h
Yield: 87 %

Procedure:
In an argon atmosphere, 3.30 g (73.2 mmol) of ethylamine was dissolved in 30 mL of hexane, and a solution obtained by dissolving 6.21 g (26.7 mmol) of Si(sBuNCHCHNsBu)(H)Cl in 5 mL of hexane was added thereto at −20° C. After stirring at room temperature for 2 hours, insoluble matters produced were separated by filtration, and the solvent was removed by distillation from the filtrate under atmospheric pressure. The obtained residue was distilled under reduced pressure (distillation temperature: 92-96° C./4.0×102 Pa) to obtain 1,3-di-sec-butyl-2-ethylamino-1,3-diaza-2-silacyclopent-4-ene (Si(sBuNCHCHNsBu)(H)NHEt) as a pale yellow liquid (yielded amount: 5.61 g, yield: 87%). This product was a mixture of a plurality of isomers differing in the steric configuration from each other.
Reaction SMILES: C(Cl)(=O)[C:2](Cl)=[O:3].[Cl:7][C:8]([Cl:14])=[C:9]([Cl:13])[C:10]([NH2:12])=[O:11]>ClC(Cl)C>[Cl:13][C:9](=[C:8]([Cl:14])[Cl:7])[C:10]([N:12]=[C:2]=[O:3])=[O:11]
Reactant: NC(=O)C(Cl)=C(Cl)Cl
Reactant: O=C(Cl)C(=O)Cl
Solvent: CC(Cl)Cl
Product: O=C=NC(=O)C(Cl)=C(Cl)Cl
Temperature: 2 °C
Reaction time: 1 h

Procedure:
260 ml of oxalyl chloride were added to 225 g of trichloroacrylamide in 525 ml of dichloroethane cooled to 2°C and the mixture was held at 0°C for 1 hour and then refluxed for 16 hours. The resulting solution was evaporated under reduced pressure and the residue was distilled to obtain 232 g of trichloroacryloyl-isocyanate boiling at 86°C under 20 mm Hg and having a refractive index nD23 = 1.538.
Reaction SMILES: F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH3:13][C:14]1([CH3:20])[CH2:19][NH:18][CH2:17][CH2:16][NH:15]1.C(N(C(C)C)C(C)C)C>CC(N(C)C)=O>[CH3:13][C:14]1([CH3:20])[NH:15][CH2:16][CH2:17][N:18]([C:2]2[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=2)[CH2:19]1
Reactant: CC1(C)CNCCN1
Reactant: CCOC(=O)c1ccc(F)cc1
Solvent: CC(=O)N(C)C
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)c1ccc(N2CCNC(C)(C)C2)cc1
Temperature: 200 °C
Yield: 55.3 %

Procedure:
Ethyl 4-fluorobenzoate (0.151 mL, 1 mmol), 2,2-dimethylpiperazine (0.137 g, 1.20 mmol) and N-ethyl-N-propan-2-ylpropan-2-amine (0.349 mL, 2.00 mmol) were dissolved in DMA (2 mL) and sealed into a microwave tube. The reaction was heated to 200° C. for 4 h in the microwave reactor and cooled to room temperature. The crude mixture was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 3.5M ammonia in methanol, fractions were evaporated to dryness to afford an oil. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 10% 2M ammonia/MeOH in DCM. Pure fractions were evaporated to dryness to afford ethyl 4-(3,3-dimethylpiperazin-1-yl)benzoate (0.145 g, 55.3%) as a white solid. 1H NMR (399.9 MHz, CDCl3) δ 1.15 (6H, d), 1.37 (3H, t), 2.38 (1H, d), 2.41 (1H, d), 2.96-3.04 (2H, m), 3.65-3.69 (2H, m), 4.33 (2H, q), 6.84-6.87 (2H, m), 7.89-7.93 (2H, m). MS: m/z 266 (MH+).
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1.[Si:13](Cl)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].P([O-])([O-])([O-])=O>C1COCC1>[Si:13]([O:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][OH:3])=[CH:7][CH:8]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]
Reactant: OCCc1ccc(O)cc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: O=P([O-])([O-])[O-]
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)Oc1ccc(CCO)cc1
Reaction time: 1.25 h
Yield: 71.8 %

Procedure:
Sodium hydride (60% dispersion in mineral oil, 145 mg) was added portionwise to a solution of 4-(2-hydroxyethyl)phenol (502 mg) in THF (15 ml) and the mixture was stirred at 20° C. for 30 min. tert-Butyldimethylsilyl chloride (547 mg) was added and the mixture was stirred for 75 min. Phosphate buffer solution (pH 6.5) was added and the mixture was extracted with EtOAc. The combined extracts were dried (Na2SO4) and the solvent evaporated in vacuo to give a residue which was purified by SPE (10 g). Elution with DCM-cyclohexane (1:3) then DCM then EtOAc gave the title compound (658 mg). LCMS RT=3.62 min.