Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:7]2[C:12]([C:13](=[O:26])[C:14]=1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([O:24]C)=[O:23])=[CH:18][CH:17]=1)=[CH:11][CH:10]=[C:9]([Cl:27])[CH:8]=2)=[O:4].[Li+].[OH-]>CO>[CH3:1][O:2][C:3]([C:5]1[N:6]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:7]2[C:12]([C:13](=[O:26])[C:14]=1[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([OH:24])=[O:23])=[CH:18][CH:17]=1)=[CH:11][CH:10]=[C:9]([Cl:27])[CH:8]=2)=[O:4]
Reactant: COC(=O)c1ccc(Cc2c(C(=O)OC)n(-c3ccccc3)c3cc(Cl)ccc3c2=O)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: COC(=O)c1c(Cc2ccc(C(=O)O)cc2)c(=O)c2ccc(Cl)cc2n1-c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 36.6 %

Procedure:
A mixture of 7-chloro-3-(4-methoxycarbonyl-benzyl)-4-oxo-1-phenyl-1,4-dihydro-quinoline-2-carboxylic acid methyl ester (compound 10, 31 mg) and LiOH (1 M aq, 1 mL) in MeOH (10 mL) was stirred at RT overnight. The reaction mixture was then stirred at 50° C. for 3 h, then extracted with EtOAc. The organic layer was separated, the aqueous layer acidified by adding AcOH (aq), and the resulting mixture extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified by preparative TLC (hexane/acetone, 70:30+1% AcOH) to afford 11 mg of 3-(4-carboxybenzyl)-7-chloro-4-oxo-1-phenyl-1,4-dihydroquinoline-2-carboxylic acid methyl ester as an off-white solid. MS=447; MP=258.0-261.0° C.
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:3]=1[CH2:16][CH2:17]Cl.[CH:19]1([NH2:24])[CH2:23][CH2:22][CH2:21][CH2:20]1>CN(C)C=O>[CH:19]1([N:24]2[C:2]3[N:7]4[N:8]=[CH:9][CH:10]=[C:6]4[N:5]=[C:4]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:3]=3[CH2:16][CH2:17]2)[CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: NC1CCCC1
Reactant: CCOC(=O)c1nc2ccnn2c(Cl)c1CCCl
Solvent: CN(C)C=O
Product: CCOC(=O)c1nc2ccnn2c2c1CCN2C1CCCC1
Temperature: 25 °C
Yield: 85.2 %

Procedure:
In 48 ml of anhydrous dimethylformamide were dissolved 3.60 g (12.50 mmol) of ethyl 7-chloro-6-(2-chloro-ethyl)-pyrazolo[1,5-a]pyrimidine-5-carboxylate, and 7.3 ml (d=0.863, 73.99 mmol) of cyclopentylamine were added at once to the solution while stirring at room temperature under a nitrogen atmosphere, and the mixture was stirred for additional 1 hour and 20 minutes under the same conditions. The reaction mixture was then poured into 250 ml of ice water. Insoluble solids were collected by filtration, washed with water and air-dried to obtain 3.20 g (yield: 85.3%) of the intended product.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:11])[CH3:10])=[CH:5][CH:4]=1.[Cl:12][C:13]1[CH:14]=[C:15]([C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])[CH:16]=[C:17]([Cl:19])[CH:18]=1.C(N(CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[Cl:12][C:13]1[CH:14]=[C:15]([C:20]([OH:25])([C:21]([F:22])([F:23])[F:24])[CH2:10][C:9]([C:6]2[CH:7]=[CH:8][C:3]([S:2][CH3:1])=[CH:4][CH:5]=2)=[O:11])[CH:16]=[C:17]([Cl:19])[CH:18]=1
Reactant: CSc1ccc(C(C)=O)cc1
Reactant: O=C(c1cc(Cl)cc(Cl)c1)C(F)(F)F
Solvent: Cc1ccccc1
Solvent: CCCCN(CCCC)CCCC
Product: CSc1ccc(C(=O)CC(O)(c2cc(Cl)cc(Cl)c2)C(F)(F)F)cc1
Temperature: 60 °C
Reaction time: 15 h
Yield: 45.5 %

Procedure:
0.50 g (3.01 mmol) of 1-(4-(methylthio)phenyl)ethanone, 0.73 g of (3.01 mmol) of 3′,5′-dichloro-2,2,2-trifluoroacetophenone, 1.46 g of toluene and 0.17 g (0.90 mmol) of tributylamine were fed and the mixture was stirred for 15 hours at 60° C. After leaving the reaction mixture for one night at room temperature, separation operation was performed by adding 30 ml of ethyl acetate and 10 ml of water, and the ethyl acetate phase was washed with diluted aqueous solution of hydrochloric acid. After removing the solvent by distilling under reduced pressure, the residue was purified by silica gel column chromatography to obtain 0.56 g of 3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-hydroxy-1-(4-(methylthio)phenyl)butan-1-one (yield 45.2%).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.Cl.[C:22]([O:26][C:27]([C@H:29]1[CH2:36][C:33]2([CH2:35][CH2:34]2)[CH2:32][NH:31][C@@H:30]1[C:37](O)=[O:38])=[O:28])([CH3:25])([CH3:24])[CH3:23].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[CH3:1][C:2]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:37]([C@@H:30]3[C@@H:29]([C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:28])[CH2:36][C:33]4([CH2:34][CH2:35]4)[CH2:32][NH:31]3)=[O:38])=[CH:18][CH:19]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: Cc1cc(COc2ccc(N)cc2)c2ccccc2n1
Reactant: CC(C)(C)OC(=O)[C@H]1CC2(CC2)CN[C@@H]1C(=O)O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: Cc1cc(COc2ccc(NC(=O)[C@H]3NCC4(CC4)C[C@@H]3C(=O)OC(C)(C)C)cc2)c2ccccc2n1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
4-(2-Methylquinolin-4-ylmethoxy)phenylamine as an HCl salt (94.0 mg, 0.28 mmol) and (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2.5]octane-6-carboxylic acid (70.0 mg, 0.27 mmol) were dissolved in DMF (2.0 mL). BOP (143.0 mg, 0.32 mmol) was added to the above solution and then cooled to 0° C. Diisopropylethylamine (0.175 mL, 1.0 mmol) was added to the above mixture at 0° C. and then the reaction was stirred at room temperature for 2 h. The mixture was diluted with water, extracted with ethyl acetate, the combined extract was washed with brine, dried and concentrated. The crude tert-butyl(6S,7S)-6-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2.5]octane-7-carboxylate (140 mg) was used in the next step without purification. ESI (M+H)+502.4.
Reaction SMILES: CC(C)(OC([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[CH2:12][S:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][N:18]1[C:26](=[O:27])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]1=[O:28])=O)C.BrC1C=CC2C(NC(=O)C2(C=CCC)C=1)=O.C1(=O)NC(=O)C2=CC=CC=C12.[ClH:57].O1CCOCC1>C(Cl)Cl>[ClH:57].[NH:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[CH2:12][S:13][CH2:14]/[CH:15]=[CH:16]\[CH2:17][N:18]1[C:26](=[O:27])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]1=[O:28]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1CSC/C=C\CN1C(=O)c2ccccc2C1=O
Agent: CCC=CC12C=C(Br)C=CC1C(=O)NC2=O
Agent: Cl
Agent: O=C1NC(=O)c2ccccc21
Solvent: C1COCCO1
Solvent: ClCCl
Product: O=C1c2ccccc2C(=O)N1C/C=C\CSC[C@@H]1CCCN1
Temperature: 25 °C
Reaction time: 3 h
Yield: 92 %

Procedure:
To a solution of (S,Z)-2-[4-[[[1-[(1,1-dimethylethoxy)carbonyl]-2-pyrrolidinyl]methyl]thio]-2-butenyl]-1H-isoindole-1,3(2H)-dione, (prepared as in Example I, Part A, except substituting 4-bromo-2-butenyl phthalimide for the corresponding phthalimide) (3.60 mmol)) in 2 mL of CH2Cl2 was added 18 mL of 4N HCl/dioxane at 0° C. The ice bath was removed and the reaction was stirred at room temperature for 3 hrs. The reaction mixture was concentrated in vacuo to give title compound (92% yield).
Reaction SMILES: C1(NC(N)=S)C=CC=CC=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH3:28])=[S:20])=[C:14]([OH:29])[C:13]=1[S:30]([N:33]([CH3:35])[CH3:34])(=[O:32])=[O:31].[Si:36](Cl)([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37].N1C=CN=C1>>[CH3:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[NH:21][C:19]([NH:18][C:15]1[CH:16]=[CH:17][C:12]([Cl:11])=[C:13]([S:30]([N:33]([CH3:34])[CH3:35])(=[O:32])=[O:31])[C:14]=1[O:29][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])=[S:20]
Reactant: Cc1ccccc1NC(=S)Nc1ccc(Cl)c(S(=O)(=O)N(C)C)c1O
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: NC(=S)Nc1ccccc1
Agent: c1c[nH]cn1
Product: Cc1ccccc1NC(=S)Nc1ccc(Cl)c(S(=O)(=O)N(C)C)c1O[Si](C)(C)C(C)(C)C
Yield: 57.4 %

Procedure:
Following the general procedure for protected phenyl thiourea formation outlined in example 12, N-[4-Chloro-2-hydroxy-3-[N″,N″-dimethylaminosulfonyl]phenyl]-N′-(2-methylphenyl)thiourea (557 mg, 1.39 mmol), tert-butyldimethylsilyl chloride (1.04 mg, 6.95 mmol) and imidazole (189 mg, 2.78 mmol) were reacted to form the desired product (410 mg, 57%). EI-MS m/z 514.2 (M+).
Reaction SMILES: Cl[C:2]1[C:11]2[CH:10]=[C:9]3[N:12]=[CH:13][N:14]=[C:8]3[CH2:7][C:6]=2[N:5]=[CH:4][C:3]=1[C:15]#[N:16].[Br:17][C:18]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:19]=1[NH2:20].Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(OCCO)C>[Br:17][C:18]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:19]=1[NH:20][C:2]1[C:11]2[CH:10]=[C:9]3[N:12]=[CH:13][N:14]=[C:8]3[CH2:7][C:6]=2[N:5]=[CH:4][C:3]=1[C:15]#[N:16]
Reactant: N#Cc1cnc2c(c1Cl)C=C1N=CN=C1C2
Reactant: Nc1ccc(Cl)cc1Br
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCCO
Solvent: c1ccncc1
Product: N#Cc1cnc2c(c1Nc1ccc(Cl)cc1Br)C=C1N=CN=C1C2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 22.8 %

Procedure:
A mixture of 0.25 g (1.10 mmol) of 8-chloroimidazo[4,5-g]quinoline-7-carbonitrile, 0.27 g (1.3 mmol) of 2-bromo-4-chloroaniline, and 0.13 g (1.12 mmol) of pyridine hydrochloride in 7.0 mL of 2-ethoxyethanol is heated at reflux temperature for 1 hour, cooled to room temperature, poured into a saturated solution of sodium bicarbonate and stirred for 0.5 hour. The solid is collected by filtration, washed with water and dried. The solid is purified by silica gel chromatography utilizing a gradient of methylene chloride/methanol(97:3 to 90:10) to yield 0.10 g of 8-(2-bromo-4-chlorophenylamino)imidazo[4,5-g]quinoline-7-carbonitrile as an yellow solid, mp 244-246° C. (shrinks at 200° C.).
Reaction SMILES: [C:1]1([O:11][CH2:12][CH2:13][CH2:14]Br)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[CH:20][CH:19]=1.C(N(CC)CC)C.[OH-].[Na+].[Cl-].[Na+]>O.O1CCCC1>[CH3:16][O:17][C:18]1[CH:19]=[CH:20][C:21]([N:24]2[CH2:29][CH2:28][N:27]([CH2:14][CH2:13][CH2:12][O:11][C:1]3[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH:4]=[CH:3][CH:2]=3)[CH2:26][CH2:25]2)=[CH:22][CH:23]=1
Reactant: BrCCCOc1cccc2ccccc12
Reactant: COc1ccc(N2CCNCC2)cc1
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1ccc(N2CCN(CCCOc3cccc4ccccc34)CC2)cc1
Yield: 67.7 %

Procedure:
10.6 g (40 mMol) 1-(naphth-1-yloxy)-3-bromopropane were mixed with 7.7 g (40 mMol) 1-(4-methoxyphenyl)-piperazine, 8.1 g (80 mMol) anhydrous triethylamine and 40 ml. anhydrous tetrahydrofuran and the reaction mixture subsequently maintained at reflux temperature for 10 hours. After cooling, the precipitated triethylamine hydrobromide was filtered off with suction. The filtrate was substantially evaporated in a vaccum, the residue was taken up in chloroform and the solution obtained was shaken with dilute aqueous sodium hydroxide solution, then with an aqueous solution of sodium chloride and thereafter with water. The organic phase was dried over anhydrous sodium sulfate, filtered through active charcoal and finally freed from chloroform in a vacuum. The oily residue was brought to crystallization by the addition of isopropanol. After recrystallization from methanol, with the addition of active charcoal, there were obtained 10.2 g (68% of theory) 1-(4-methoxyphenyl)-4-[3-(naphth-1-yloxy)-propyl]-piperazine, which had a melting point of 68° - 69° C. The corresponding hydrochloride was obtained by passing dry hydrogen chloride through a dioxan solution of the base. It had a melting point of 235° - 238° C.
Reaction SMILES: [CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:11](=[CH:12][NH:13][N:14]=2)[CH:10]=[C:9]([CH3:16])[C:8]=1[NH:17][C:18]([C:20]1[N:21]([C:27]2[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][N:28]=2)[N:22]=[C:23]([O:25][CH3:26])[CH:24]=1)=[O:19])=[O:6])([CH3:3])[CH3:2].[N:34]1[C:41]([F:42])=[N:40][C:38](F)=[N:37][C:35]=1[F:36].C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:11](=[CH:12][N:13]([C:38]3[N:40]=[C:41]([F:42])[N:34]=[C:35]([F:36])[N:37]=3)[N:14]=2)[CH:10]=[C:9]([CH3:16])[C:8]=1[NH:17][C:18]([C:20]1[N:21]([C:27]2[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][N:28]=2)[N:22]=[C:23]([O:25][CH3:26])[CH:24]=1)=[O:19])=[O:6])([CH3:3])[CH3:2]
Reactant: Fc1nc(F)nc(F)n1
Reactant: COc1cc(C(=O)Nc2c(C)cc3c[nH]nc3c2C(=O)NC(C)C)n(-c2ncccc2Cl)n1
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: COc1cc(C(=O)Nc2c(C)cc3cn(-c4nc(F)nc(F)n4)nc3c2C(=O)NC(C)C)n(-c2ncccc2Cl)n1
Temperature: 20 °C
Reaction time: 3 h

Procedure:
To a solution of 6-{[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazole-3-carbonyl]-amino}-5-methyl-2H-indazole-7-carboxylic acid isopropyl amide (0.300 g, 0.641 mmol) in chloroform (2.0 ml) was added cyanuryl fluoride (2,4,6-trifluoro-1,3,5-triazine) (0.220 g, 1.669 mmol) followed by triethylamine (0.090 ml, 0.046 mmol). The reaction mixture was stirred at 20° C. for three hours, then evaporated to dryness and submitted to high vacuum. The residue was taken up in a small amount of chloroform and separated from some less soluble material, then evaporated to give the compound showing the physical data described in the table under P.43.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:17][NH:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=1>>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([N:18]([CH3:17])[CH2:19][CH2:20][C:21]3[CH:22]=[CH:23][C:24]([N+:27]([O-:29])=[O:28])=[CH:25][CH:26]=3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=C1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Reactant: CNCCc1ccc([N+](=O)[O-])cc1
Product: CN(CCc1ccc([N+](=O)[O-])cc1)C1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Yield: 52.5 %

Procedure:
2.4 g (10.9 mmol) of 1-(4-nitrophenyl)-4-piperidone and 2.0 g (10.9 mmol) of N-methyl-N-(2-(4-nitrophenyl)ethyl)amine were reacted in a similar manner to Example 1. 2.2 g of 1-(4-nitrophenyl)-4-(N-methyl-N-(2-(4-nitrophenyl)ethyl)amino)piperidine were obtained. Melting point 97°-98° C.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([I:21])[N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@@:12]2([CH3:20])[OH:13])=[C:4]([O:22]C)[N:3]=1.C(N(CC)C(C)C)C.[Na+].[I-].C[Si](Cl)(C)C.C(N(CC)CC)C>C(#N)C>[NH2:1][C:2]1[NH:3][C:4](=[O:22])[C:5]2[N:6]=[C:7]([I:21])[N:8]([C@H:11]3[C@@:12]([OH:13])([CH3:20])[C@H:14]([OH:15])[C@@H:16]([CH2:18][OH:19])[O:17]3)[C:9]=2[N:10]=1
Reactant: COc1nc(N)nc2c1nc(I)n2[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)O
Agent: CCN(CC)C(C)C
Agent: C[Si](C)(C)Cl
Agent: [I-]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1n1c(I)nc2c(=O)[nH]c(N)nc21
Reaction time: 16 h

Procedure:
This compound can be synthesized from 2-amino-8-iodo-6-methoxy-9-(2-C-methyl-β-D-ribofuranosyl)purine using procedures familiar to one skilled in the art. For example: To a solution of 2-amino-8-iodo-6-methoxy-9-(2-C-methyl-β-D-ribofuranosyl)purine (XV)(1 mmol) in acetonitrile (3.0 mL) under nitrogen is added diethylisopropyl amine (52 mL, 0.3 mmol), followed by the addition of NaI (99 mg, 0.5 mmol) and TMSCl (64 mL, 0.5 mmol). The contents are stirred under nitrogen for 16 h. After completion of the reaction (monitoring by TLC), triethyl amine (30 mL, 0.3 mmol) are added. The reaction is concentrated under vacuum, and the solids are dissolved in methanol/water mixture (1.5 mL, 0.5 mL) and are stirred for 15 min.
Reaction SMILES: [Br:1][C:2]([CH2:4][CH2:5][O:6][CH:7]([O:9][CH2:10][CH3:11])[CH3:8])=[CH2:3].[OH-].[K+].[CH:14]([Br:17])(Br)[Br:15].[Br-].[Br-].C([N+](C)(C)CC[N+](CC1C=CC=CC=1)(C)C)C1C=CC=CC=1>C(Cl)Cl.O>[Br:15][C:14]1([Br:17])[CH2:3][C:2]1([Br:1])[CH2:4][CH2:5][O:6][CH:7]([O:9][CH2:10][CH3:11])[CH3:8]
Reactant: BrC(Br)Br
Reactant: C=C(Br)CCOC(C)OCC
Agent: C[N+](C)(CC[N+](C)(C)Cc1ccccc1)Cc1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: CCOC(C)OCCC1(Br)CC1(Br)Br
Reaction time: 24 h
Yield: 68.5 %

Procedure:
To a solution of 14.02 g (0.0628 mol) 2-bromo-4-(1-ethoxy-ethoxy)-but-1-ene in 108 ml methylene chloride with 0.5-0.9 ml 45% aqueous potassium hydroxide was added 16.4 ml (0.118 mol) of bromoform and 2.88 g (0.00628 mol) of N,N′-dibenzyl-N,N,N′,N′-tetramethylethylenediammonium dibromide and 28 ml (0.314 mol) 45% aqueous potassium hydroxide. After 3 days the reaction mixture was poured onto water. The resulting mixture was transferred to a separatory funnel and the phases were separated. To the isolated organic layer was added 2.88 g (0.00628 mol) of N,N′-dibenzyl-N,N,N′,N′-tetramethylethylenediammonium dibromide and 28 ml (0.314 mol) 45% aqueous potassium hydroxide. After 24 hours, hexanes and water were added. This mixture was gravity filtered through qualitative fluted filter paper. The resulting mixture was transferred to a separatory funnel and the phases were separated. The organic layer was dried over MgSO4 and filtered. The solvent was removed from the filtrate in vacuo to yield 17.0 g of 1,1,2-tribromo-2-[2-(1-ethoxy-ethoxy)-ethyl]-cyclopropane as an oil.
Reaction SMILES: [C:1]([O:5][C:6](/[C:8](=[CH:15]\[C:16](\[CH3:31])=[CH:17]\[CH:18]([CH3:30])[CH2:19][CH:20]([CH3:29])[CH2:21][CH:22]([CH3:28])[CH2:23][CH:24]([CH3:27])[CH2:25][CH3:26])/[CH2:9][CH:10]([CH3:14])[C:11]([OH:13])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.ClCCl>[CH3:14][CH:10]([CH2:9]/[C:8](=[CH:15]/[C:16](/[CH3:31])=[CH:17]/[CH:18]([CH3:30])[CH2:19][CH:20]([CH3:29])[CH2:21][CH:22]([CH3:28])[CH2:23][CH:24]([CH3:27])[CH2:25][CH3:26])/[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:11]([O:13][CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[O:12]
Reactant: CCC(C)CC(C)CC(C)CC(C)/C=C(C)/C=C(/CC(C)C(=O)O)C(=O)OC(C)(C)C
Reactant: CC(C)(C)OC(=O)CO
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CCC(C)CC(C)CC(C)CC(C)/C=C(C)/C=C(/CC(C)C(=O)OCC(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 96 h
Yield: 72.1 %

Procedure:
(Step 1) To Compound 8 (16 mg, 0.037 mmol), dichloromethane (1.8 mL), tert-butyl 2-hydroxyacetate (5.8 mg, 0.044 mmol), EDC.HCl (10.5 mg, 0.055 mmol), and DMAP (0.4 mg, 0.0037 mmol) were added, and the resulting mixture was stirred at room temperature for 4 days. The solvent was evaporated under reduced pressure, and the resulting residue was purified by thin-layer column chromatography (ethyl acetate/n-hexane=1/9), whereby 1-(2-tert-butoxy-2-oxoethyl) 5-tert-butyl (Z)-2-methyl-4-{(E)-2,4,6,8,10-pentamethyldodec-2-enylidene}pentanedioate (14.7 mg, 73%) was obtained.
Reaction SMILES: [N:1]([CH2:4][CH:5]1[CH2:9][C:8]2[CH:10]=[C:11]([CH2:20][CH3:21])[CH:12]=[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:7]=2[O:6]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>>[CH2:20]([C:11]1[CH:12]=[C:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:7]2[O:6][CH:5]([CH2:4][NH2:1])[CH2:9][C:8]=2[CH:10]=1)[CH3:21]
Reactant: CCc1cc2c(c(-c3ccccc3)c1)OC(CN=[N+]=[N-])C2
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCc1cc2c(c(-c3ccccc3)c1)OC(CN)C2
Yield: 4 %

Procedure:
To a solution of 4-ethylphenol (10.0 g, 82.0 mmol) in acetonitrile (250 mL) cooled to 0° C. was slowly added N-bromosuccinimide (16.0 g, 90 mmol) and the reaction mixture was allowed to stir at 0° C. for 1 h. The solvent was removed in vacuo and the reaction mixture was diluted with ice water (500 mL) and diethyl ether (500 mL). A solid precipitate was removed via filtration and the aqueous phase was separated and extracted with ethyl ether (2×200 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:9) gave 8.35 g (51%). Treatment of 2-bromo-4-ethylphenol (8.35 g, 41.0 mmol) with potassium carbonate (14.3 g, 100 mmol) and allyl bromide (6.57 g, 130 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 2-allyl-6-bromo-4-ethylphenol. Treatment of 2-allyl-6-bromo-4-ethylphenol (5.18, 22.0 mmol) with 3-chloroperoxybenzoic acid (8.60 g, 33.0 mmol, 77%) followed by potassium carbonate (7.4 g, 55.0 mmol) generally according to the procedure described for Intermediate 9 afforded 3.94 g (70%) of (±)-(7-bromo-5-ethyl-2,3-dihydro-1-benzofuran-2-yl)methanol. Treatment of (±)-(7-bromo-5-ethyl-2,3-dihydro-1-benzofuran-2-yl)methanol (3.94 g, 15.0 mmol) with p-toluenesulfonyl chloride (3.5 g, 18.0 mol) generally according to the procedure described for Intermediate 10 gave 5.78 g (92%) of (±)-(7-bromo-5-ethyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Treatment of (±)-(7-bromo-5-ethyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.73 mmol) and 2-methylphenylboronic acid (0.30 g, 2.19 mmol) generally according to the procedure described for Intermediate 35 afforded 0.30 g, (97%) of (±)-(5-ethyl-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.23 g, 3.55 mmol) generally according to the procedure described for Intermediate 98 afforded 0.16 g (77%) of (±)-2-(azidomethyl)-5-ethyl-7-phenyl-2,3-dihydro-1-benzofuran. Treatment of (±)-2-(azidomethyl)-5-ethyl-7-phenyl-2,3-dihydro-1-benzofuran with polymer-supported triphenylphosphine (0.786 g, 0.869 mmol) according to the procedure described in Example 154 afforded 0.009 g (4%) of (±)-[(5-ethyl-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine as a white solid, hydrochloride salt. mp 198° C. (dec).
Reaction SMILES: [OH:1][CH:2]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:3][NH:4][C:5](=O)[CH2:6][CH2:7][CH2:8][CH2:9][C:10]([NH:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21]CC2C=CC=CC=2)=[C:17]([O:29]CC2C=CC=CC=2)[CH:16]=1)=O.B#B.CO>O1CCCC1>[OH:1][CH:2]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:3][NH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][NH:12][CH2:13][CH2:14][C:15]1[CH:16]=[C:17]([OH:29])[C:18]([OH:21])=[CH:19][CH:20]=1
Reactant: O=C(CCCCC(=O)NCC(O)c1ccccc1)NCCc1ccc(OCc2ccccc2)c(OCc2ccccc2)c1
Agent: B#B
Solvent: CO
Solvent: C1CCOC1
Product: Oc1ccc(CCNCCCCCCNCC(O)c2ccccc2)cc1O

Procedure:
A solution of N-(2-hydroxy-2-phenylethyl)-N'-[2-(3,4-bis(phenylmethoxy)phenyl)ethyl]hexane-1,6-diamide prepared in an analogous manner to that described in Example 12(a) above (3.48 g) in dry tetrahydrofuran (100 ml) was stirred under a nitrogen atmosphere whilst diborane in tetrahydrofuran (30 ml of 1M solution) was added and then the solution heated to reflux for 6 hours. Methanol (100 ml) was added to the cooled solution and the mixture evaporated to dryness. The residue was dissolved in methanolic HCl (100 ml) and heated to reflux for 18 hours. The solution was evaporated to dryness and the residue recrystallised from ethanol to give the title compound, as the dihydrochloride salt, colorless prisms (1.3 g) mp 188°-9°.