Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:22]=[CH:21][C:5]2[N:6]([CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[C:7]([CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[N:8][C:4]=2[CH:3]=1.C(N(CC)C(C)C)(C)C.[SH:32][CH2:33][C:34]([O:36][CH3:37])=[O:35].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:11][C:10]([CH3:13])([CH3:12])[CH2:9][C:7]1[N:6]([CH2:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[CH:21]=[CH:22][C:2]([S:32][CH2:33][C:34]([O:36][CH3:37])=[O:35])=[CH:3][C:4]=2[N:8]=1
Reactant: CC(C)(C)Cc1nc2cc(Br)ccc2n1CC1CCOCC1
Reactant: COC(=O)CS
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)CSc1ccc2c(c1)nc(CC(C)(C)C)n2CC1CCOCC1
Temperature: 25 °C
Yield: 99.3 %

Procedure:
A mixture of 5-bromo-2-(2,2-dimethylpropyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole (Step C, 300 mg, 0.82 mmol), N,N-diisopropylethylamine (286 μL, 1.64 mmol), methyl mercaptoacetate (73 μL, 0.82 mmol), tris(dibenzylideneacetone)dipalladium(0) (37.5 mg, 0.041 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (47.4 mg, 0.082 mmol) in 1,4-dioxane was microwaved at 120° C. for 30 min. The reaction mixture was cooled to room temperature and filtered through a pad of celite. The filtrate was concentrated and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=3:2 then 1:1 as eluent) to afford the title compound (318 mg, 99%) as a yellow viscous oil.
Reaction SMILES: C(N=[N+]=[N-])C1C=CC=CC=1.[N:11]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[N+:12]=[N-:13].[C:23]([C:25]1[S:26][C:27]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[C:28]([CH3:30])[N:29]=1)#[CH:24]>>[F:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][CH2:14][N:11]2[CH:24]=[C:23]([C:25]3[S:26][C:27]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[C:28]([CH3:30])[N:29]=3)[N:13]=[N:12]2)=[CH:17][CH:18]=1
Reactant: [N-]=[N+]=NCCc1ccc(F)cc1
Reactant: C#Cc1nc(C)c(C(=O)OCC)s1
Agent: [N-]=[N+]=NCc1ccccc1
Product: CCOC(=O)c1sc(-c2cn(CCc3ccc(F)cc3)nn2)nc1C
Yield: 82 %

Procedure:
Following the procedure as described in Example 2, making variations as necessary to replace benzylazide with 1-(2-azidoethyl)-4-fluorobenzene to react with ethyl 2-ethynyl-4-methylthiazole-5-carboxylate, the title compound was obtained as a white solid in 82% yield: 1H NMR (300 MHz, CDCl3) δ 7.87 (s, 1H), 7.09-6.98 (m, 2H), 6.98-6.89 (m, 2H), 4.59 (t, J=7.2 Hz, 2H), 4.30 (q, J=7.1 Hz, 2H), 3.20 (t, J=7.2 Hz, 2H), 2.68 (s, 3H), 1.34 (t, J=7.1 Hz, 3H); MS (ES+) m/z 361.3 (M+1).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[C:10]1([C:16]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:17][CH2:18]O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>>[C:10]1([C:16]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:17][CH2:18][O:1][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: O=Cc1ccc(O)cc1
Reactant: OCCC(c1ccccc1)(c1ccccc1)c1ccccc1
Product: O=Cc1ccc(OCCC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1

Procedure:
By the method of example 12, 4-hydroxybenzaldehyde was condensed with 3,3,3-triphenylpropanol to provide 4-(3,3,3-triphenylpropoxy)benzaldehyde, a white solid, mp 127°-130° C. after recrystallization from hexane (58% yield). This material (4.0 g, 10.2 mmol) was suspended in ethanol (100 mL), and sodium borohydride (0.2 g, 5.0 mmol) was added. After 3 hr, aqueous 1N HCl was added dropwise until gas evolution ceased. Precipitated boric acid was removed by filtration, and the filtrate concentrated to a gummy residue. This was partitioned between water and ether, and the ether solution dried (MgSO4), filtered, and concentrated. The residue was kept under high vacuum overnight to remove solvent, leaving 4-(3,3,3-triphenylpropoxy)benzyl alchohol as an amorphous solid (3.9 g, 97%). This material (3.9 g, 9.9 mmol) was dissolved in benzene (80 mL), and thionyl chloride (1.0 mL, 14 mmol) was added, followed by five drops of DMF at 5-minute intervals. The mixture was heated briefly to reflux, cooled, and concentrated to an oil which solidified on standing. Trituration of the solid with cold methanol provided 4-(3,3,3-triphenylpropoxy)benzyl chloride as a white powder, mp 91°-95° C. (83%). 1H NMR (CDCl3) δ 7.19-7.35 (m, 17H), 6.66 (d, J=8.7 Hz, 2H), 4.51 (s, 2H), 3.72 (t, J=7.8 Hz, 2H), 3.12 (t, J=7.8 Hz, 2H).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:11])([CH3:10])[CH3:9])=[CH:4][C:3]=1[CH2:12][NH:13][S:14]([OH:17])(=[O:16])=[O:15].[I:18]Cl>O.O1CCCC1.Cl>[OH:1][C:2]1[C:7]([I:18])=[CH:6][C:5]([C:8]([CH3:11])([CH3:10])[CH3:9])=[CH:4][C:3]=1[CH2:12][NH:13][S:14]([OH:17])(=[O:16])=[O:15]
Reactant: CC(C)(C)c1ccc(O)c(CNS(=O)(=O)O)c1
Reactant: ClI
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)c1cc(I)c(O)c(CNS(=O)(=O)O)c1
Temperature: 20 °C
Reaction time: 2 h

Procedure:
To a solution of 2-hydroxy-5-(1,1-dimethylethyl)phenylmethanesulfamic acid (2.6 g., 0.01 mole) in water-tetrahydrofuran (5:1; v:v; 90 ml.) is added a freshly prepared solution of iodine monochloride (1.64 g., 0.01 mole) in 3 N hydrochloric acid (12 ml.) portionwise over 5 minutes providing a dark reaction solution which is stirred at 20° C. for 2 hours and then cooled to 0°-5° C. The resulting insoluble solid is collected, washed with 12 N hydrochloric acid, dried with aspiration at 20° C. and washed with water to give crude 2-hydroxy-3-iodo-5-(1,1-dimethylethyl)phenylmethanesulfamic acid (3.3 g., 85.9%), m.p. 172°-180° C. with dec. Recrystallization from water-ethanol (10:1; v:v) provides pure 2-hydroxy-3-iodo-5-(1,1-dimethylethyl)phenylmethanesulfamic acid as colorless crystals, m.p. 180°-182° C. with dec.
Reaction SMILES: [C:1]([C:4]1[C:21]([OH:22])=[CH:20][CH:19]=[CH:18][C:5]=1[O:6][CH2:7][CH:8]([OH:17])[CH2:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:3])[CH3:2].[O-:23][CH2:24][CH3:25].[Na+].[Na].C([OH:30])C>C(OCC)(=O)C(OCC)=O.C1C=CC=CC=1.CCOCC>[C:24]([C:25]1[O:22][C:21]2[C:4]([C:1](=[O:3])[CH:2]=1)=[C:5]([O:6][CH2:7][CH:8]([OH:17])[CH2:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH:18]=[CH:19][CH:20]=2)([OH:30])=[O:23]
Reactant: CC[O-]
Reactant: CC(=O)c1c(O)cccc1OCC(O)COc1ccccc1
Reactant: CCO
Agent: [Na+]
Agent: [Na]
Solvent: c1ccccc1
Solvent: CCOC(=O)C(=O)OCC
Solvent: CCOCC
Product: O=C(O)c1cc(=O)c2c(OCC(O)COc3ccccc3)cccc2o1

Procedure:
A solution of 1-(2-acetyl-3-hydroxyphenoxy)-2-hydroxy-3-phenoxypropane (12.08 g) in diethyl oxalate (30 ml) was added to a suspension of sodium ethoxide, prepared from sodium (6.0 g) and ethanol (60 ml), in benzene (100 ml). The mixture was heated under reflux for 1.5 hours, cooled and poured into ether. The precipitated yellow solid was collected, washed with ether and dried. The solid was then added to a mixture of glacial acetic acid (80 ml) and concentrated hydrochloric acid (30 ml) and heated under reflux for 1 hour. After cooling, the reaction mixture was poured with stirring into cold water (1 L). The precipitated gum was washed with water by decantation and solidified by trituration with acetic acid. Recrystallization from acetic acid gave 1-(2-carboxychromon-5-yloxy)-2-hydroxy-3-phenoxypropane (7.0 g) as a white powder, m.p. 88°-90° C.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:17](Cl)(=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19]>C(Cl)Cl.CCOC(C)=O>[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:7][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:4][CH:3]=1
Reactant: NCc1ccc(N)cc1
Reactant: CC(C)(C)C(=O)Cl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)C(=O)NCc1ccc(N)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 55.1 %

Procedure:
To a 0° C. solution of 2.5 ml (22 mmol) 4-aminobenzylamine in 100 mL CH2Cl2 was added 3 mL (22 mmol) triethylamine and 2.7 mL (22 mmol) pivaloyl chloride slowly by syringe over 5 min. and the reaction mixture was warmed to room temperature and stirred 1 hour. Additional portions of. triethylamine (0.4 ml )and pivaloyl chloride (0.4 ml) were added and the reaction mixture was allowed to stir 16 hours. The reaction mixture was then diluted with 400 mL EtOAc, washed with 400 mL each of, saturated aqueous NaHCO3, water, and brine, then dried over Na2SO4, filtered and concentrated. The residue was purified by washing with 100 mL EtOAc, and extracting this wash with 2×100 mL 1N HCl. The combined aqueous extracts were brought to pH>10 with 6M NaOH and extracted 3×100 mL EtOAc. The combined EtOAc extracts were then dried over Na2SO4, filtered and concentrated to give 2.5 g N-(4-amino-benzyl)-2,2-dimethyl-propionamide as a off-white solid. 1H NMR (300 mHz, CDCl3) δ 7.15 (d, 2H); 6.65 (d, 2H); 5.75 (b s, 1H); 4.30 (d, 2H); 3.65 (b s, 2H); 1.20 (s, 9H).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.[CH:9]1([C:13]#[N:14])[CH2:12][CH2:11][CH2:10]1.C1(C)C=CC=CC=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>CCOC(C)=O.O>[F:8][C:4]1[N:3]=[C:2]([C:9]2([C:13]#[N:14])[CH2:12][CH2:11][CH2:10]2)[CH:7]=[CH:6][CH:5]=1
Reactant: N#CC1CCC1
Reactant: Fc1cccc(F)n1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: Cc1ccccc1
Product: N#CC1(c2cccc(F)n2)CCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 64.7 %

Procedure:
To a 0° C. solution of 2,6-difluoropyridine (5.0 g, 43 mmol), cyclobutanecarbonitrile (3.5 g, 43 mmol), and toluene (100 mL) was added sodium hexamethyldisilazide (NaHMDS, 2.0 M in THF, 24 mL, 47 mmol). The resulting mixture was warmed to rt and stirred for 2 h. The mixture was then diluted with EtOAc (200 mL) and water (100 mL). The aqueous layer was extracted with EtOAc and the combined organic phases were washed with brine, dried over Na2SO4, concentrated, and purified using silica gel chromatography to provide the desired product (4.9 g) as a colorless oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[O:9][C:10]([F:13])([F:12])[F:11].[Cl:14]N1C(=O)CCC1=O>C(#N)C>[Br:1][C:2]1[C:3]([O:9][C:10]([F:12])([F:11])[F:13])=[CH:4][C:5]([NH2:8])=[C:6]([Cl:14])[CH:7]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: Nc1ccc(Br)c(OC(F)(F)F)c1
Solvent: CC#N
Product: Nc1cc(OC(F)(F)F)c(Br)cc1Cl
Temperature: 60 °C
Yield: 61.8 %

Procedure:
To a mixture of 4-bromo-3-trifluoromethoxy-phenylamine (2.0 g, 7.8 mmol) in ACN (60 mL) was slowly added a solution of N-chlorosuccinimide (1.0 g, 7.8 mmol) in ACN (40 mL). The reaction mixture was heated at 60° C. overnight and extracted with ethyl acetate/water. The organic layer was dried over sodium sulfate and purified by flash chromatography (40 g column, 100% hexanes to 10% EtOAc: hexanes) to produce the desired product as an orange-ish_colored oil (1.4 g, 64% yield).
Reaction SMILES: Cl.O1CCOCC1.C(OC([NH:15][C:16]1[CH:41]=[CH:40][C:19]([CH2:20][NH:21][C:22]2[C:32]3[CH2:31][CH2:30][N:29]([C:33](=[O:38])[C:34]([F:37])([F:36])[F:35])[CH2:28][CH2:27][C:26]=3[CH:25]=[CH:24][C:23]=2[Cl:39])=[CH:18][CH:17]=1)=O)(C)(C)C.C(OCC)C>O1CCOCC1.C(Cl)Cl>[ClH:39].[NH2:15][C:16]1[CH:17]=[CH:18][C:19]([CH2:20][NH:21][C:22]2[C:32]3[CH2:31][CH2:30][N:29]([C:33](=[O:38])[C:34]([F:37])([F:35])[F:36])[CH2:28][CH2:27][C:26]=3[CH:25]=[CH:24][C:23]=2[Cl:39])=[CH:40][CH:41]=1
Reactant: CC(C)(C)OC(=O)Nc1ccc(CNc2c(Cl)ccc3c2CCN(C(=O)C(F)(F)F)CC3)cc1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Solvent: CCOCC
Product: Nc1ccc(CNc2c(Cl)ccc3c2CCN(C(=O)C(F)(F)F)CC3)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 229.2 %

Procedure:
Add 4M hydrogen chloride in dioxane (20 mL, 20 mmol) to a solution of 6-(4-tert-butoxycarbonylamino-benzylamino)-7-chloro-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]-azepine (0.219, 0.44 mmol) in 1,4-dioxane/DCM (1:1, 40 mL). Stir overnight at room temperature, add diethyl ether and concentrate in vacuo to obtain the title compound (0.219 g, 100%) that was dried in vacuo.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22](Cl)(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2.[S:26]1[CH:30]=[C:29]([NH2:31])[N:28]=[CH:27]1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CCOC(C)=O.CCCCCCC>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22]([NH:31][C:29]3[N:28]=[CH:27][S:26][CH:30]=3)(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2
Reactant: Nc1cscn1
Reactant: O=S(=O)(Cl)c1ccc2c(c1)OCCN2c1ccc(C(F)(F)F)cc1Br
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCCCCCC
Product: O=S(=O)(Nc1cscn1)c1ccc2c(c1)OCCN2c1ccc(C(F)(F)F)cc1Br
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 21.3 %

Procedure:
A round-bottom flask was charged with 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (INTERMEDIATE C, 299.84 mg, 0.657 mmol), thiazol-4-amine (79 mg, 0.788 mmol), and THF (3283 n1) to give a brown mixture. The flask was cooled in an ice-bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1379 μl, 1.379 mmol) was added dropwise over 30 s. After 30 min, the cooling bath was removed, and the mixture was allowed to warm to room temperature. The reaction mixture was quenched by the addition of aq. 1N hydrochloric acid and a small amount of brine and extracted with EtOAc (3×, emulsion). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography on a 40 g column with 0 to 10% MeOH/DCM. The desired product was repurified again by chromatography on a 40 g silica gel column, this time with 0 to 40% EtOAc/Heptane to give 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-4-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (73.1 mg, 0.140 mmol) as a cream-colored solid. 1H NMR (400 MHz, DMSO-d6) δ=10.88 (s, 1 H), 8.88 (d, J=2.2 Hz, 1 H), 8.20 (d, J=1.5 Hz, 1 H), 7.89 (dd, J=1.6, 8.5 Hz, 1 H), 7.73 (d, J=8.4 Hz, 1 H), 7.25 (d, J=2.2 Hz, 1 H), 7.16 (dd, J=2.2, 8.6 Hz, 1 H), 6.96 (d, J=2.2 Hz, 1 H), 6.22 (d, J=8.6 Hz, 1 H), 4.36 (d, J=15.8 Hz, 2 H), 3.78-3.63 (m, 2 H). m/z (ESI) 520.2 (M+H)+.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([OH:8])=[O:7].[Cl:9][CH2:10]OCCl.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)(Cl)Cl>[Cl:9][CH2:10][C:5]1[S:1][C:2]([C:6]([OH:8])=[O:7])=[CH:3][CH:4]=1
Reactant: O=C(O)c1cccs1
Reactant: ClCOCCl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClC(Cl)Cl
Product: O=C(O)c1ccc(CCl)s1

Procedure:
2-Thiophenecarboxylic acid is treated in a solution of chloroform with chloromethyl ether in the presence of 0.9 to 2.2 equivalents of aluminum chloride to give 5-chloromethyl-2-thienylcarboxylic acid. Treatment of the obtained acid with excess thionyl chloride at room temperature for about 16 hours yields the acid chloride with is reacted with diazomethane to give the corresponding diazoketone. A methanol solution of the diazoketone is irradiated under nitrogen for about one hour with a high pressure mercury lamp using a Quarz filter. The methyl 5-chloromethyl-2-thienylacetate is obtained upon work up and column chromatography on silica gel. The acetate is hydrolyzed by treatment of a 1:1 mixture of acetic acid and concentrated hydrochloric acid at room temperature overnight to give 5-chloromethyl-2-thienylacetic acid.
Reaction SMILES: CN1CCCC1=O.Br[C:9]1[C:14](=[O:15])[CH:13]=[C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:11]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:10]=1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[F:34][C:35]([F:40])([F:39])C([O-])=O.[Na+]>O>[C:22]1([N:11]2[C:12]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:13][C:14](=[O:15])[C:9]([C:35]([F:40])([F:39])[F:34])=[C:10]2[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: O=c1cc(-c2ccccc2)n(-c2ccccc2)c(-c2ccccc2)c1Br
Reactant: O=C([O-])C(F)(F)F
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=c1cc(-c2ccccc2)n(-c2ccccc2)c(-c2ccccc2)c1C(F)(F)F
Temperature: 160 °C
Yield: 20.4 %

Procedure:
To 40 ml of 1-methyl-2-pyrrolidinone were added 2.0 g (0.0050 mole) of 3-bromo-1,2,6-triphenyl-4(1H)-pyridinone, 2.7 g (0.020 mole) of sodium trifluoroacetate and 1.9 g (0.010 mole) of cuprous iodide. The reaction mixture was then heated at 160° C. for 5 hours in a nitrogen atmosphere. After allowing the reaction mixture to cool down, it was poured into water, followed by extraction with ethyl ether. The organic layer (the extract) was washed with 50 ml of a saturated aqueous solution of sodium hydrogen carbonate. After washing the organic layer further with water, it was dried over anhydrous sodium sulfate. Subsequent to removal of the sodium sulfate, the solvent was distilled off, and the residue was crystallized from a 1:3 mixed solvent of ethyl acetate and hexane to yield 0.4 g of 1,2,6-triphenyl-3-trifluoromethyl-4(1H)-pyridinone having a melting point of 222°-225° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[S:5][C:6]=1Br.[Si]([O:20][CH2:21][CH2:22][CH2:23]I)(C(C)(C)C)(C)C>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[S:5][C:6]=1[CH2:23][CH2:22][CH2:21][OH:20]
Reactant: CC(C)(C)[Si](C)(C)OCCCI
Reactant: Brc1cc(C2OCCO2)sc1Br
Solvent: C1CCOC1
Product: OCCCc1sc(C2OCCO2)cc1Br
Temperature: -78 °C
Reaction time: 8 h
Yield: 44 %

Procedure:
2-(4,5-Dibromo-2-thienyl)-1,3-dioxolane (for a synthesis, see J Org Chem, 1976, 41, 8) (6.05 g, 19.2 mmol) was dissolved in dry THF (500 ml) and cooled to −78° C. After 15 min the reaction mixture was treated with 3-(tert-butyldimethylsilyloxy)-1-iodopropane (6.3 g, 1.1 equiv.) (for a synthesis, see J. Chem. Soc. Perkin Trans. 1, 1190, 1111). After a further 15 min. the cooling bath was removed and the reaction allowed warm to room temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride, and partitioned between ethyl acetate and water. The organic phase was dried over anhydrous magnesium sulphate and evaporated. The residue was chromatographed on silica gel eluting with 0-10% ethyl acetate in hexane. Product-containing fractions were combined and evaporated to a colourless oil) 5.61 g. This was dissolved in THF (100 ml) and treated with tetra-n-butyl ammonium fluoride (2M solution in THF, 16 ml) and stirred at room temperature overnight. The solvent was evaporated and the residue partitioned between water and ethyl acetate. The organic phase was separated, washed with brine, dried over anhydrous magnesium sulphate and evaporated. The residue was chromatographed on silica gel eluting with 1-100% ethyl acetate in hexane, to afford the title compound (2.48 g, 44%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:14]([C:17]2[CH:22]=[C:21]([N+]([O-])=O)[C:20]([OH:26])=[C:19]([N+:27]([O-:29])=[O:28])[CH:18]=2)([CH3:16])[CH3:15])[CH:7]=[C:8]([N+]([O-])=O)[C:9]=1[OH:10])([O-:3])=[O:2].[N+](C1C(O)=C([N+]([O-])=O)C([N+]([O-])=O)=C(C(C2C=CC(O)=CC=2)(C)C)C=1[N+]([O-])=O)([O-])=O.OC1C=CC(C(C2C=CC(O)=CC=2)(C)C)=CC=1.[N+]([O-])(O)=O.ClC(Cl)C>>[OH:26][C:20]1[CH:21]=[CH:22][C:17]([C:14]([C:6]2[CH:7]=[CH:8][C:9]([OH:10])=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)([CH3:16])[CH3:15])=[CH:18][C:19]=1[N+:27]([O-:29])=[O:28]
Reactant: CC(C)(c1cc([N+](=O)[O-])c(O)c([N+](=O)[O-])c1)c1cc([N+](=O)[O-])c(O)c([N+](=O)[O-])c1
Agent: CC(C)(c1ccc(O)cc1)c1c([N+](=O)[O-])c([N+](=O)[O-])c(O)c([N+](=O)[O-])c1[N+](=O)[O-]
Agent: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Solvent: CC(Cl)Cl
Solvent: O=[N+]([O-])O
Product: CC(C)(c1ccc(O)c([N+](=O)[O-])c1)c1ccc(O)c([N+](=O)[O-])c1

Procedure:
This invention uses 2,2-bis(3,5-dinitro-4-hydroxyphenyl) propane as a polymerization inhibitor. For the sake of convenience, this compound will also be called tetranitrobisphenol A. A method of synthesizing said compound is described in Stroganov et al, Zh. Org. Khim 1973, 9(8), 1713-17, and Smirnov and Stroganov USSR Pat. No. 237,860 (1969). Thus, 2,2-bis(4-hydroxyphenyl)propane is nitrated with a concentrated nitric acid (for instance 70% HNO3) in a suitable solvent such as dichloroethane to afford primarily 2,2-bis(4-hydroxy-3-nitro-phenyl)propane. A typical reaction condition for this step is 20°-30° C. for 2 hours. Without isolating the product, a mixture of sulfuric acid and nitric acid (for instance, 42% H2SO4, 50% HNO3, and 8% H2O) is added to the reaction mixture and nitration continued to afford tetranitrobisphenol A. A typical reaction condition for the second step is 40° C. for 2 hours. The desired product is isolated by a routine procedure.
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+].Cl[CH2:16][CH2:17][O:18][CH3:19]>CN(C=O)C.O>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH2:16][CH2:17][O:18][CH3:19]
Reactant: COCCCl
Reactant: Oc1ccccc1Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: COCCOc1ccccc1Br
Temperature: 90 °C
Yield: 59.9 %

Procedure:
To a solution of 2-bromophenol (500.0 mg, 2.89 mmol) in DMF (5 mL) was added cesium carbonate (2.82 g, 8.67 mmol). To this mixture was added 1-chloro-2-methoxyethane (0.26 mL, 2.89 mmol, Aldrich) and the mixture was heated at 90° C. for 4 h. After completion, the reaction mixture was diluted with water (3 mL) and extracted with ethyl acetate (2×10 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to get 1-bromo-2-(2-methoxyethoxyl)benzene (400 mg, 60.2%) as clear liquid that was used as such for next step without any purification. 1H NMR (400 MHz, DMSO) δ 7.57 (dd, J=7.9, 1.5 Hz, 1H), 7.39-7.24 (m, 1H), 7.13-7.05 (m, 1H), 6.89 (td, J=7.7, 1.2 Hz, 1H), 4.17 (t, J=4.6 Hz, 2H), 3.69 (t, J=4.6 Hz, 2H), 3.33 (s, 3H). MS (ESI, positive ion) m/z: 231.08 (M+1).
Reaction SMILES: [C:1]([NH:4][C:5]1[N:6]([CH3:20])[C:7]2[C:12]([C:13]=1[CH2:14][C:15]([O:17]CC)=[O:16])=[CH:11][CH:10]=[CH:9][CH:8]=2)(=[O:3])[CH3:2].CO.ClCCl.[OH-].[Na+]>C(O)(=O)C>[C:1]([NH:4][C:5]1[N:6]([CH3:20])[C:7]2[C:12]([C:13]=1[CH2:14][C:15]([OH:17])=[O:16])=[CH:11][CH:10]=[CH:9][CH:8]=2)(=[O:3])[CH3:2]
Reactant: CCOC(=O)Cc1c(NC(C)=O)n(C)c2ccccc12
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: CO
Product: CC(=O)Nc1c(CC(=O)O)c2ccccc2n1C
Reaction time: 8 h

Procedure:
To a solution of 3.7 g. of 2-acetamido-3-carbethoxymethyl-1-methylindole in 37 ml. of methanol and 5 ml. of dichloromethane, 15.5 ml. of 1N sodium hydroxide are added at 0° C. The mixture is allowed to stand overnight and then it is neutralized with acetic acid and then evaporated to dryness. The oily residue is taken up with diluted hydrochloric acid and the solid which forms is washed with water. The product is purified by crystallization from ethanol. Yield 3.07 g., m.p. 200°-206° C.
Reaction SMILES: [CH3:1][N:2]([CH3:19])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]=[CH:10][C:11]2[N:16]=[C:15](O)[CH:14]=[C:13]([CH3:18])[N:12]=2)=[CH:5][CH:4]=1.O=P(Cl)(Cl)[Cl:22]>>[Cl:22][C:15]1[CH:14]=[C:13]([CH3:18])[N:12]=[C:11](/[CH:10]=[CH:9]/[C:6]2[CH:7]=[CH:8][C:3]([N:2]([CH3:19])[CH3:1])=[CH:4][CH:5]=2)[N:16]=1
Reactant: Cc1cc(O)nc(C=Cc2ccc(N(C)C)cc2)n1
Reactant: O=P(Cl)(Cl)Cl
Product: Cc1cc(Cl)nc(/C=C/c2ccc(N(C)C)cc2)n1
Yield: 17.8 %

Procedure:
In analogy to example 12c), by heating 2-[2-(4-dimethylamino-phenyl)-vinyl]-6-methyl-pyrimidin-4-ol (2 g, 7.8 mmol) in POCl3 (14.3 ml, 157 mmol) at 130° C. for 4.5 h there was obtained (E)-4-chloro-2-[2-(4-dimethylamino-phenyl)-vinyl]-6-methyl-pyrimidine (0.38 g, 18.5%) as a dark oil. EI mass spectrum, m/e: 273 (M calculated for C15H16ClN3: 273).