Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[NH:10][C:9]1=[NH:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:18]([O:20][C:21](=[O:33])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:29][CH2:30][CH2:31]Cl)[CH:23]=1)[CH3:19]>CC(=O)CC>[CH2:18]([O:20][C:21](=[O:33])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:29][CH2:30][CH2:31][N:10]2[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:9]2=[NH:17])[CH:23]=1)[CH3:19]
Reactant: N=c1[nH]c2ccccc2n1Cc1ccccc1
Reactant: CCOC(=O)c1cccc(OCCCCl)c1
Solvent: CCC(C)=O
Product: CCOC(=O)c1cccc(OCCCn2c(=N)n(Cc3ccccc3)c3ccccc32)c1
Temperature: 85 °C
Yield: 74.1 %

Procedure:
To a solution of 1-benzyl-1,3-dihydro-benzoimidazol-2-ylideneamine (247 mg, 1.10 mmol) in 2-butanone (40 ml) was added 3-(3-chloro-propoxy)-benzoic acid ethyl ester (0.40 g, 1.65 mmol) and KI (0.55 g, 3.32 mmol). The reaction was heated to 85° C. where it was maintained for 54 h. After this time, the mixture was cooled to rt and filtered. The filtrate was concentrated under reduced pressure and combined with the collected solid, washed with diethyl ether and petroleum ether and dried to provide 3-[3-(3-benzyl-2-imino-2,3-dihydro-benzoimidazol-1-yl)-propoxy]-benzoic acid ethyl ester (350 mg, 74%). HPLC-MS 430 [M+1]+.
Reaction SMILES: [NH2:1][C:2]1[C:7]2=[C:8]([Br:24])[CH:9]=[C:10]([CH:11]3CCN(C(OC(C)(C)C)=O)[CH2:13][CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.NC1C2=CC=C(C([OH:38])CC)N2N=CN=1>>[NH2:1][C:2]1[C:7]2=[C:8]([Br:24])[CH:9]=[C:10]([CH:11]([OH:38])[CH2:12][CH3:13])[N:6]2[N:5]=[CH:4][N:3]=1
Reactant: CCC(O)c1ccc2c(N)ncnn12
Reactant: CC(C)(C)OC(=O)N1CCC(c2cc(Br)c3c(N)ncnn23)CC1
Product: CCC(O)c1cc(Br)c2c(N)ncnn12

Procedure:
This compound was prepared in a manner similar to the bromination procedure described for the preparation of tert-butyl 4-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)piperidine-1-carboxylate, using 1-(4-amino-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-propan-1-ol as the starting material. 1H NMR (300 MHz, DMSO-d6) δ 7.78 (s, 1H), 7.59 (broad s, 6.80 (d, 1H), 6.52 (d, 1H), 5.11 (d, 1H), 4.98 to 4.93 (m, 1H), 1,83 to 1.66 (m, 2H), 0.84 (t, 3H); ES-MS m/z 271.3/273.1 [M+H]+, RT (min) 1.86.
Reaction SMILES: [C:1](=[N:32]O)([C:8]1[CH:31]=[CH:30][C:11]([C:12](=[N:28]O)[C:13]2[CH:18]=[CH:17][C:16]([C:19](=[N:26]O)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H]>C(O)C.N.[Ni]>[NH2:26][CH:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:16]1[CH:15]=[CH:14][C:13]([CH:12]([NH2:28])[C:11]2[CH:30]=[CH:31][C:8]([CH:1]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[NH2:32])=[CH:9][CH:10]=2)=[CH:18][CH:17]=1
Reactant: [H][H]
Reactant: ON=C(c1ccccc1)c1ccc(C(=NO)c2ccc(C(=NO)c3ccccc3)cc2)cc1
Agent: [Ni]
Agent: N
Solvent: CCO
Product: NC(c1ccccc1)c1ccc(C(N)c2ccc(C(N)c3ccccc3)cc2)cc1

Procedure:
The trioxime from Step 2 (3 g) is dissolved in ethyl alcohol (250 ml) saturated with ammonia gas and Raney nickel W-6 (2 g) added. The mixture is subjected to 500 psi hydrogen pressure and heated to 90° for two hours. The catalyst is removed by filtration and 220 ml ethyl alcohol by distillation. A pale yellow crystalline material is filtered and dried.
Reaction SMILES: [NH3:1].[Cl:2][C:3]1[CH:8]=[C:7](Cl)[N:6]=[C:5]([C:10]2[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])[N:4]=1>O1CCCC1>[Cl:2][C:3]1[N:4]=[C:5]([C:10]2[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][C:11]=2[O:17][CH3:18])[N:6]=[C:7]([NH2:1])[CH:8]=1
Reactant: COc1ccc(Cl)cc1-c1nc(Cl)cc(Cl)n1
Reactant: N
Solvent: C1CCOC1
Product: COc1ccc(Cl)cc1-c1nc(N)cc(Cl)n1
Temperature: 0 °C
Yield: 71 %

Procedure:
A pressure bottle was charged with tetrahydrofuran (50 ml) and cooled to 0° C. Ammonia gas was passed through the tetrahydrofuran until saturated. To this solution was added 4,6-dichloro-2-(5-chloro-2-methoxy-phenyl)-pyrimidine (0.15 g, 0.52 mmol) and the mixture was heated at 75-80° C. for 18 hours. Evaporation of volatiles under reduced pressure provided the hydrochloride salt of 6-chloro-2-(5-chloro-2-methoxy-phenyl)-pyrimidin-4-yl-amine (0.10 g, 71%).
Reaction SMILES: Cl[C:2]1[C:3]2[N:11]=[N:10][N:9]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]4([OH:23])[CH2:22][CH2:21][CH2:20]4)[N:14]=3)[C:4]=2[N:5]=[C:6]([NH2:8])[N:7]=1.[CH3:24][C:25]1[N:26]=[CH:27][S:28][CH:29]=1>>[CH3:24][C:25]1[N:26]=[C:27]([C:2]2[C:3]3[N:11]=[N:10][N:9]([CH2:12][C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([C:19]5([OH:23])[CH2:22][CH2:21][CH2:20]5)[N:14]=4)[C:4]=3[N:5]=[C:6]([NH2:8])[N:7]=2)[S:28][CH:29]=1
Reactant: Cc1cscn1
Reactant: Nc1nc(Cl)c2nnn(Cc3cccc(C4(O)CCC4)n3)c2n1
Product: Cc1csc(-c2nc(N)nc3c2nnn3Cc2cccc(C3(O)CCC3)n2)n1

Procedure:
This is prepared from 7-chloro-3-(6-[1-hydroxycyclobutyl]pyrid-2-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine and 4-methylthiazole by the method of Example 38.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:5]([C:4]2[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=2)=[O:7])=[CH:14][CH:13]=1
Reactant: Nc1ccccc1
Reactant: O=C(O)c1cccc(F)c1
Product: Nc1ccc(C(=O)c2cccc(F)c2)cc1
Reaction time: 1 h
Yield: 299.2 %

Procedure:
To stirred 90° C. polyphosphoric acid (150 g) was added 10.72 g (7.65 mmol) of 3-fluorobenzoic acid and 6.98 g (7.5 mmol) of aniline and the bath temperature raised to 180°-190° C. and held there for 1 hour. A solution was obtained at about 130° C. The heating bath was removed and the stirred mixture (sublimate above the solution) was treated cautiously with 60 mL of water. The mixture was stirred at 140°-155° C. for 1 hour, the heating bath removed, 50 mL of 3N HCl added, the mixture poured into 750 mL of water and filtered through a pad of Celite. The filtrate was basified with 15% sodium hydroxide and the resulting solid extracted with methylene chloride. The dried (MTSO4) solution was filtered and the solvent removed to yield a brown solid. Recrystallization from ethanol-hexane (1:3) returned a greenish yellow solid that was chromatographed on silica gel (methylene chloride) to yield 4.83 g (30%) of yellow 4-amino-3'-fluorobenzophenone, mp 98°-100° C. 1H NMR (300 MHz, CDCl3): 4.21 (s, 2H, NH2) 6.66-6.70 (m, 2H, aromatic) 7.23-7.26 (m, 1H, aromatic) 7.39-7.51 (m, 3H, aromatic) 7.69-7.72 (m, 2H, aromatic). MS (CI, CH4): 216 (M+1).
Reaction SMILES: Cl[C:2]1[C:11]([C:12]#[N:13])=[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:20])[CH:8]=2)[N:3]=1.[CH2:21]([NH:23][CH2:24][CH3:25])[CH3:22]>>[Cl:20][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([N:23]([CH2:24][CH3:25])[CH2:21][CH3:22])[C:11]([C:12]#[N:13])=[C:10]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCNCC
Reactant: N#Cc1c(Cl)nc2ccc(Cl)cc2c1-c1ccccc1
Product: CCN(CC)c1nc2ccc(Cl)cc2c(-c2ccccc2)c1C#N

Procedure:
The title compound was prepared in analogy to example 27 step C from 2,6-dichloro-4-phenyl-quinoline-3-carbonitrile (prepared as described in example 27 step B) and diethylamine. Yellow solid. MS (ESI): 336.2 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]2[CH:11]=[C:12]([OH:15])[CH:13]=[CH:14][C:8]=2[CH:7]=1)=[O:5])[CH3:2].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26](O)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([O:15][C:12]2[CH:13]=[CH:14][C:8]3[CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[S:10][C:9]=3[CH:11]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]
Reactant: CCOC(=O)c1cc2ccc(O)cc2s1
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCOC(=O)c1cc2ccc(OC3CCN(C(=O)OC(C)(C)C)CC3)cc2s1
Yield: 94.4 %

Procedure:
The above prepared 6-hydroxy-benzo[b]thiophene-2-carboxylic acid ethyl ester (0.206 g, 0.927 mmol, see example 7, step 1 and 2) was dissolved in 5 mL of THF and treated successively at −10° C. with 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.261 g, 1.4 eq.), triphenylphosphine (0.340 g, 1.4 eq.) and DIAD (0.255 mL, 2 eq.), and the mixture then kept at ambient temperature over night. Pouring onto crashed ice, twofold extraction with AcOEt, washing with water and brine, drying over magnesium sulfate, and evaporation of the solvents, followed by flash chromatography (SiO2, hexane AcOEt=85/15), yielded 0.355 g of the title compound as colorless gum.
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14]I)([CH3:4])([CH3:3])[CH3:2].[CH2:17]([O:24][C:25]1[CH:30]=[C:29](I)[CH:28]=[CH:27][C:26]=1[N:32]1[S:36](=[O:38])(=[O:37])[N:35]([CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:34](=[O:45])[CH2:33]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[C:1]([O:5][C:6](=[O:16])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][C:29]1[CH:28]=[CH:27][C:26]([N:32]2[CH2:33][C:34](=[O:45])[N:35]([CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[S:36]2(=[O:38])=[O:37])=[C:25]([O:24][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:30]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: C[Si](C)(C)CCN1C(=O)CN(c2ccc(I)cc2OCc2ccccc2)S1(=O)=O
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCCC[C@H]1CI
Product: CC(C)(C)OC(=O)N[C@@H]1CCCC[C@H]1Cc1ccc(N2CC(=O)N(CC[Si](C)(C)C)S2(=O)=O)c(OCc2ccccc2)c1

Procedure:
The title compound is prepared from ((1R*,2R*)-2-iodomethylcyclohexyl)-carbamic acid tert-butyl ester and 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one analogous to the method used in Example 57, step B.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[CH:10]=[C:11]([C:13]([OH:15])=O)[N:12]=1.N=C=N.[F:26][C:27]([F:39])([F:38])[C:28]1[CH:33]=[CH:32][C:31]([S:34]([NH2:37])(=[O:36])=[O:35])=[CH:30][CH:29]=1>CN(C1C=CN=CC=1)C.ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[CH:10]=[C:11]([C:13]([NH:37][S:34]([C:31]2[CH:30]=[CH:29][C:28]([C:27]([F:26])([F:39])[F:38])=[CH:33][CH:32]=2)(=[O:35])=[O:36])=[O:15])[N:12]=1
Reactant: O=C(O)c1cn(-c2ccc(Cl)cc2)c(-c2ccccc2Cl)n1
Reactant: NS(=O)(=O)c1ccc(C(F)(F)F)cc1
Agent: CN(C)c1ccncc1
Agent: N=C=N
Solvent: ClCCl
Product: O=C(NS(=O)(=O)c1ccc(C(F)(F)F)cc1)c1cn(-c2ccc(Cl)cc2)c(-c2ccccc2Cl)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 9.7 %

Procedure:
In a 20-mL screw-cap vial, 250 mg (0.75 mmol) 2-(2-chlorophenyl)-1-(4-chlorophenyl)-1H-imidazole-4-carboxylic acid, 18.3 mg DMAP (0.15 mmol), 1.25 g PS-Carbodimide (1.5 mmol) (polystyrene-supported cyclohexylcarbodiimide, Argonaut Technologies Inc., San Carlos, Calif.), 169 mg α,α,α-trifluoro-p-toluenesulfonamide (0.75 mmol), and 12 mL dichloromethane were added, and the reaction mixture was mixed by orbital shaking at rt overnight. The reaction mixture was filtered through a filter tube (polypropylene frit), and the filtrate was evaporated under reduced pressure. The crude product was redissolved in 2 mL MeOH and purified by preparative HPLC to give 39.3 mg of N-{[2-(2-chlorophenyl)-1-(4-chlorophenyl)-1H-imidazol-4-yl]carbonyl}-4-(trifluoromethyl)benzenesulfonamide (beige solid, 10% yield). 1H NMR (400 MHz, CD3COCD3) δ 8.25 (d, 2 H), 7.85 (s, 1 H), 7.75 (s, 2H), 7.20-7.40 (m, 6 H), 6.95 (t, 2 H); LC-MS m/z 540 (MH+), retention time 3.36 min (method 2).
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:8]2[CH:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][C:10](=O)[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.P(Br)(Br)([Br:21])=O.C(=O)(O)[O-].[Na+].O>ClCCl>[Br:21][C:10]1[CH2:11][CH:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:8]([C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[N:9]=1
Reactant: CCOC(=O)C1CC(=O)NN1c1ncccc1Cl
Reactant: O=P(Br)(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)C1CC(Br)=NN1c1ncccc1Cl
Temperature: 83 °C
Reaction time: 0.08 h
Yield: 95 %

Procedure:
A 1-L four-necked flask equipped with a mechanical stirrer, thermometer, reflux condenser, and nitrogen inlet was charged with acetonitrle (400 mL), ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate (i.e. the product of Step A) (50.0 g, 0.185 mol) and phosphorus oxybromide (34.0 g, 0.119 mol). The orange slurry was heated to reflux at 83° C. over a period of 20 minutes. The resulting turbid, orange solution was held at reflux for 75 minutes, at which time a dense, tan, crystalline precipitate had formed, The reflux condenser was replaced with a distillation head, and a cloudy, colorless distillate (300 mL) was collected. A second 1-L four-necked flask equipped with a mechanical stirrer was charged with sodium bicarbonate (45 g, 0.54 mol) and water (200 mL). The concentrated reaction mixture was added to the sodium bicarbonate slurry over a period of 5 minutes. The resulting two-phase mixture was stirred vigorously for 5 minutes, at which time gas evolution had ceased. The mixture was diluted with dichloromethane (200 mL) and then was stirred for 75 minutes. The mixture was treated with 5 g of Celite® 545 diatomaceous filter aid and then filtered to remove a brown, tarry substance. The filtrate was transferred to a separatory funnel. The brown organic layer (400 mL) was separated and then was treated with magnesium sulfate (15 g) and Darco® G60 activated charcoal (2.0 g). The resulting slurry was stirred magnetically for 15 minutes and then filtered to remove the magnesium sulfate and charcoal. The green filtrate was treated with silica gel (3 g) and stirred for several minutes. The deep blue-green silica gel was removed by filtration, and the filtrate was concentrated on a rotary evaporator. The product consisted of a light amber oil (58.6 g, 95% yield), which crystallized upon standing. The only appreciable impurity observed by 1H NMR was 0.3% acetonitrile.
Reaction SMILES: C[C:2]1([C:17]2[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=2)[C:6]2[C:7]([CH3:14])=[C:8]([OH:13])[C:9]([CH3:12])=[C:10]([CH3:11])[C:5]=2[O:4][C:3]1([CH3:16])[CH3:15].Br[CH2:27][C:28]1[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[C:30](C)[CH:29]=1>>[CH:23]([C:20]1[CH:21]=[CH:22][C:17]([CH:2]2[C:6]3[C:7]([CH3:14])=[C:8]([O:13][CH2:27][C:28]4[CH:29]=[CH:30][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:36][CH:37]=4)[C:9]([CH3:12])=[C:10]([CH3:11])[C:5]=3[O:4][C:3]2([CH3:16])[CH3:15])=[CH:18][CH:19]=1)([CH3:25])[CH3:24]
Reactant: Cc1c(C)c2c(c(C)c1O)C(C)(c1ccc(C(C)C)cc1)C(C)(C)O2
Reactant: COC(=O)c1ccc(CBr)cc1C
Product: COC(=O)c1ccc(COc2c(C)c(C)c3c(c2C)C(c2ccc(C(C)C)cc2)C(C)(C)O3)cc1
Yield: 82 %

Procedure:
Using methyl 3-(4-isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-ol and methyl 4-(bromomethyl)methylbenzoate, the title compound was obtained in the same manner as in Example 1.
Reaction SMILES: [CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[NH:8][C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC.[CH3:59][O:60][C:61]1[N:66]=[CH:65][C:64]([CH2:67]O)=[CH:63][CH:62]=1>C(OCC)(=O)C.O1CCCC1>[CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[N:8]([CH2:67][C:64]2[CH:65]=[N:66][C:61]([O:60][CH3:59])=[CH:62][CH:63]=2)[C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4]
Reactant: COc1ccc(CO)cn1
Reactant: CCCCc1nc(C)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCCCc1nc(C)n(Cc2ccc(OC)nc2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 81.4 %

Procedure:
A mixture of 4′-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1 g), 1,1′-(azodicarbonyl)dipiperidine (1.41 g), tributylphosphine (1.56 mL), (6-methoxypyridin-3-yl)methanol (0.58 g) and tetrahydrofuran (50 mL) was stirred at room temperature for 4 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.09 g, 81%).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[CH:4][C:3]=1[N+:14]([O-])=O.[Cl-].[NH4+]>C(O)C.O.[Fe]>[CH3:1][C:2]1[C:3]([NH2:14])=[CH:4][CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=1
Reactant: Cc1nc(N2CCOCC2)ccc1[N+](=O)[O-]
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: Cc1nc(N2CCOCC2)ccc1N
Yield: 39.5 %

Procedure:
A suspension of 4-(6-methyl-5-nitro-2-pyridinyl)morpholine (500 mg, 2.240 mmol), iron powder (375 mg, 6.72 mmol) and ammonium chloride (60 mg, 1.120 mmol) in ethanol (15 mL) and water (5 mL) was heated at reflux for 2 hours. The reaction mixture was filtered through a pad of celite and the pad washed with further ethyl acetate. The combined filtrate and washings were separated between ethyl acetate and saturated sodium bicarbonate and the organic phase was washed with water then brine. The organics were then separated, dried over magnesium sulphate and evaporated in vacuo to give the title compound (171 mg) as a pale brown solid. LCMS (2 min, formic) Rt 0.30 min, m/z (ES+) 194 (M+H).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]Br.[OH-].[Na+].O>CCO>[O:7]([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][Br:8])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: BrCCCCCCCBr
Reactant: Oc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: BrCCCCCCCOc1ccccc1
Temperature: 25 °C
Yield: 30.2 %

Procedure:
Phenol (3.10 g, 33 mmol), 1,7-dibromoheptane (7.74 g, 30 mmol) and NaOH (1.34 g, 33 mmol) were refluxed in EtOH (40 mL) for 30 h. After cooling to room temperature, water (150 mL) was added and the mixture was extracted with ethyl acetate (4×50 mL). The organic phase was washed with water (50 mL) and brine (50 mL), and the mixture was dried over Na2 SO4. After evaporation of solvent, the residue was purified by Kugelrohr distillation to give 7-phenoxyheptyl bromide (2.46 g, 30%), bp 126°-130° C./0.10 torr, 1H-NMR: 1.2-1.9 (m, 10H), 3.36 (t, 2H), 3.91 (t, 2H), 6.7-7.2 (m, 5H).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]2)[N:5]=[C:4]([NH:19][CH:20]2[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]2)[N:3]=1.[CH3:30][C:31]1([CH3:53])[CH2:36][CH:35]([NH:37][CH2:38][CH2:39][NH:40][CH:41]2[CH2:46][C:45]([CH3:48])([CH3:47])[NH:44][C:43]([CH3:50])([CH3:49])[CH2:42]2)[CH2:34][C:33]([CH3:52])([CH3:51])[NH:32]1.[OH-].[Na+]>C1(C)C(C)=CC=CC=1>[CH3:47][C:45]1([CH3:48])[CH2:46][CH:41]([N:40]([C:2]2[N:3]=[C:4]([NH:19][CH:20]3[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]3)[N:5]=[C:6]([NH:8][CH:9]3[CH2:10][C:11]([CH3:18])([CH3:17])[NH:12][C:13]([CH3:16])([CH3:15])[CH2:14]3)[N:7]=2)[CH2:39][CH2:38][N:37]([CH:35]2[CH2:36][C:31]([CH3:53])([CH3:30])[NH:32][C:33]([CH3:52])([CH3:51])[CH2:34]2)[C:2]2[N:7]=[C:6]([NH:8][CH:9]3[CH2:14][C:13]([CH3:16])([CH3:15])[NH:12][C:11]([CH3:18])([CH3:17])[CH2:10]3)[N:5]=[C:4]([NH:19][CH:20]3[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]3)[N:3]=2)[CH2:42][C:43]([CH3:50])([CH3:49])[NH:44]1
Reactant: CC1(C)CC(Nc2nc(Cl)nc(NC3CC(C)(C)NC(C)(C)C3)n2)CC(C)(C)N1
Reactant: CC1(C)CC(NCCNC2CC(C)(C)NC(C)(C)C2)CC(C)(C)N1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1C
Product: CC1(C)CC(Nc2nc(NC3CC(C)(C)NC(C)(C)C3)nc(N(CCN(c3nc(NC4CC(C)(C)NC(C)(C)C4)nc(NC4CC(C)(C)NC(C)(C)C4)n3)C3CC(C)(C)NC(C)(C)C3)C3CC(C)(C)NC(C)(C)C3)n2)CC(C)(C)N1

Procedure:
21.15 g (0.05 moles) of 2-chloro-4,6-bis(2,2,6,6-tetramethyl-4-piperidylamino)-1,3,5-triazine (prepared according to example 2A), 8.45 g (0.025 moles) of 1,2-bis-(2,2,6,6-tetramethyl-4-piperidylamino)ethane, 2 g 0.05 of sodium hydroxide and 150 ml of xylene were boiled for 16 hours under stirring. After removing the reaction solvent, the residue was washed with water, dried at 100° C./l mm and crystallized from benzene.
Reaction SMILES: [CH3:1][C:2]([C:4]#[CH:5])=[CH2:3].[Li]CCCC.[CH3:11][C:12](=[O:15])[CH:13]=[CH2:14]>>[CH3:11][C:12]([OH:15])([C:5]#[C:4][C:2]([CH3:3])=[CH2:1])[CH:13]=[CH2:14]
Reactant: C#CC(=C)C
Reactant: C=CC(C)=O
Agent: [Li]CCCC
Product: C=CC(C)(O)C#CC(=C)C

Procedure:
The title compound was prepared according to the general method above by using 2-methylbut-1-en-3-yne (1.725 g, 26.09 mmol), nBuLi (18.0 mL, 28.8 mmol) and but-3-en-2-one (2.194 g, 31.30 mmol). Crude product was purified by flash chromatography (2.229 g, 16.37 mmol, 62.7%): Rf 0.28 (hexanes/Et2O, 4:1); 1H NMR (300 MHz, CDCl3) δ 6.00 (dd, J=17.1, 10.2 Hz, 1H, H-2), 5.49 (dd, J=17.1, 0.7 Hz, 1H, H-1trans), 5.25-5.32 (m, 1H, H-7), 5.18-5.25 (m, 1H, H-7), 5.11 (dd, J=10.2, 0.7 Hz, 1H, H-1 cis), 2.24 (s, 1H, —OH), 1.88 (as, 3H, H-8), 1.56 (s, 3H, H-9); 13C NMR (300 MHz, CDCl3) δ 142.0 (C-2), 126.2 (C-6), 122.1 (C-7), 113.5 (C-1), 89.9 (C-4/5), 85.9 (C-4/5), 68.5 (C-3), 29.9 (C-9), 23.4 (C-8); HRMS calcd for C9H13O (M+H)+ 137.0966. found 137.0984.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Br:12])[CH:8]=2)[C:3]=1[CH2:13][C:14]([OH:16])=[O:15].S(=O)(=O)(O)O.[CH3:22]O>>[OH:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Br:12])[CH:8]=2)[C:3]=1[CH2:13][C:14]([O:16][CH3:22])=[O:15]
Reactant: O=C(O)Cc1c(O)ccc2cc(Br)ccc12
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)Cc1c(O)ccc2cc(Br)ccc12

Procedure:
126.5 Grams of 2-hydroxy-6-bromo-1-naphthylacetic acid, 700 ml of methanol and 2 ml of concentrated sulfuric acid were stirred at room temperature for 24 hours. Then, the reaction mixture was concentrated under reduced pressure. The precipitate was collected by filtration and washed with small amounts of methanol and water to obtain 125.5 g of the desired product.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][C:7]2[N:11]([CH3:12])[N:10]=[C:9]([C:13]3[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:20])[N:8]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:25]I.O>CN(C)C=O>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH:6]([C:7]2[N:11]([CH3:12])[N:10]=[C:9]([C:13]3[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:20])[N:8]=2)[CH3:25])=[CH:4][CH:3]=1
Reactant: CI
Reactant: Cn1nc(-c2c(F)cccc2Cl)nc1Cc1ccc(Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(c1ccc(Cl)cc1)c1nc(-c2c(F)cccc2Cl)nn1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 96.5 %

Procedure:
To a solution of 1.0 g of 5-(4 chlorobenzyl)-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole in 10 ml of N,N-dimethylformamide at 0° C. was added 0.13 g of 60% sodiumhydride. After stirring at room temperature for 30 minutes, 0.42 g of methyl iodide added dropwise to the solution at 0° C. The reaction mixture was stirred at the same temperature for 1 hour and then at room temperature for 2 hours, poured into iced water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography to afford 1.0 g of 5-(4-chloro-α-methylbenzyl)-3-(2-chloro-6-fluorophenyl)-1-methyl-1H-1,2,4-triazole.