Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([OH:15])[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][C:7]=1[CH3:8].Cl[C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH3:30])=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][CH:18]=1>CN(C1C=CN=CC=1)C.ClC1C=CC=CC=1Cl>[CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:29][CH3:30])=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][CH:18]=2)[C:5]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:7]=1[CH3:8]
Reactant: Cc1cc(O)c(-c2ccccc2)nc1C
Reactant: COc1cc2nccc(Cl)c2cc1OC
Agent: CN(C)c1ccncc1
Solvent: Clc1ccccc1Cl
Product: COc1cc2nccc(Oc3cc(C)c(C)nc3-c3ccccc3)c2cc1OC
Temperature: 140 °C
Reaction time: 8 h
Yield: 92 %

Procedure:
1,2-Dichlorobenzene (4.5 ml) was added to 5,6-dimethyl-2-phenyl-pyridin-3-ol (267 mg), 4-chloro-6,7-dimethoxyquinoline (100 mg), and 4-(N,N-dimethylamino)pyridine (164 mg), and the mixture was stirred at 140° C. for 8 hr. The reaction solution was cooled to room temperature, and the solvent was then removed by distillation under the reduced pressure. Water was added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using hexane-acetone to give the title compound (159 mg, yield 92%).
Reaction SMILES: [OH:1][C:2]1[C:10]2N=NNC=2C=C[CH:3]=1.[CH:11]1(N=C=NC2CCCCC2)[CH2:16]CCC[CH2:12]1>CN(C)C=O>[CH2:2]([OH:1])[CH3:3].[CH:11]([O:1][CH:2]([CH3:3])[CH3:10])([CH3:16])[CH3:12]
Reactant: Oc1cccc2[nH]nnc12
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CN(C)C=O
Product: CC(C)OC(C)C
Product: CCO
Temperature: 5 °C

Procedure:
Then, at 20° C., 18.3 g (0.12 mol) of hydroxybenzotriazole (HOBT), 23.7 g (0.109 mol) of N-4-trifluoromethylbenzyl-N-n-propylamine and 25.6 g (0.125 mol) of dicyclohexyl-carbodiimide (DCCI) and a further 250 ml of dimethylformamide (DMF) were added. The mixture was left to react for 24 hours. It was then cooled to 5° C. and filtered. 500 ml of water were added to the filtrate and it was extracted with ethyl acetate. The combined organic phases were washed with water and saturated sodium hydrogen carbonate solution, dried with magnesium sulphate and filtered over kieselguhr/char-coal. After working up in the usual way, 50 g of colourless crystals of the title compound are obtained by crystallisation from ethanol/diisopropylether (1:1). The 3H-PAF-receptor bonding--determined using human thrombocytes--is Ki =1.8 nMol/liter. (The method used is described for example in European Patent Application 368 175).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:10]([NH:12][CH:13]2[CH2:15][CH2:14]2)=[O:11])[N:5]=[CH:4][C:3]=1[C:20](=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH:28]([NH2:30])=O.C(O)(=O)C>C(Cl)Cl.O>[CH:13]1([NH:12][C:10](=[O:11])[C:9]2[CH:16]=[CH:17][C:18]([CH3:19])=[C:7]([N:6]3[C:2]4=[N:1][CH:28]=[N:30][C:20]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)=[C:3]4[CH:4]=[N:5]3)[CH:8]=2)[CH2:15][CH2:14]1
Reactant: NC=O
Reactant: Cc1ccc(C(=O)NC2CC2)cc1-n1ncc(C(=O)c2ccccc2)c1N
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: O
Product: Cc1ccc(C(=O)NC2CC2)cc1-n1ncc2c(-c3ccccc3)ncnc21
Temperature: 160 °C
Yield: 62 %

Procedure:
The mixture of 3-(5-Amino-4-benzoyl-pyrazol-1-yl)-N-cyclopropyl-4-methyl-benzamide (72 mg, 0.20 mmol), formamide (1.0 mL, excess), and acetic acid (0.2 mL) was heated in the microwave at 160° C. for 20 min. After cooling, the mixture was diluted with CH2Cl2 and water, and the CH2Cl2 layer was separated, dried over Na2SO4, filtered and concentrated. The crude product was purified by preparatory HPLC to provide the title compound (46 mg, 62%) as a white solid. HPLC tR=2.3 min; MS m/z 370.3 [M+H]+.
Reaction SMILES: [Cl-].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]#[N:10])=[CH:5][CH:4]=1.[Cl-].Cl[C:13]1C=C([N+]#N)C=CC=1>>[Cl-:2].[C:8]1([CH3:13])[CH:3]=[CH:4][CH:5]=[C:6]([N+:9]#[N:10])[CH:7]=1
Reactant: N#[N+]c1cccc(Cl)c1
Reactant: N#[N+]c1ccc(Cl)cc1
Agent: [Cl-]
Product: Cc1cccc([N+]#N)c1

Procedure:
When these processes are repeated using variously substituted aryldiazonium salts, very variable yields of between 40 and 85% of theory are obtained. For example, p-chlorobenzenediazonium chloride gives 43%, m-chlorobenzenediazonium chloride gives 36%, m-toluenediazonium chloride gives 69%, o-chlorobenzenediazonium chloride gives 36%, p-dimethylaminobenzenediazonium chloride gives 54%, p-carbamoylbenzenediazonium chloride gives 58%, benzenediazonium chloride gives 72%, p-methoxybenzenediazonium chloride gives 80% and p-sulfobenzenediazonium chloride gives 10 to 20% of the corresponding diazosulfonate.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:12]=[C:11]([OH:13])[C:10]([C:14]#[C:15][Si](C)(C)C)=[CH:9][N:8]=1.Cl[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1.C(N(CC)CC)C.O>CN(C=O)C>[C:14]([C:10]1[C:11]([O:13][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[N:12][C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[N:8][CH:9]=1)#[CH:15]
Reactant: C[Si](C)(C)C#Cc1cnc(-c2ccccn2)nc1O
Reactant: COc1ccc(CCl)cc1
Solvent: O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: C#Cc1cnc(-c2ccccn2)nc1OCc1ccc(OC)cc1
Temperature: 80 °C
Reaction time: 8 h
Yield: 25.6 %

Procedure:
A mixture of compound 37-i (1.0 g, 3.7 mmol), 1-(chloromethyl)-4-methoxybenzene (0.7 g, 4.4 mmol), and triethylamine (1.5 g, 11.1 mmol) in DMF (10 mL) was stirred overnight at 80° C. The reaction mixture was cooled to room temperature, poured into water, and extracted with ethyl acetate. The combined organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (PE:EA=1:3) to afford compound 37-j (300 mg, 25%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.988-8.980 (s, 1H)), 8.775 (s, 1H), 8.581-8.555 (m, 1H), 8.020 (m, 1H), 7.554-7.541 (m, 1H), 7.522-7.493 (d, J=8.7 Hz, 2H), 6.924-6.895 (d, J=8.7 Hz, 2H), 5.741 (s, 2H), 3.807 (s, 1H), 3.509 (s, 1H), LC-MS (ESI): 318 [M+H]+
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:5]=2[N:6]=1.N1C=CC=CC=1.Cl[C:20]([O-:22])=[O:21].Cl>ClCCl>[CH3:12][O:11][C:7]1[C:5]2[N:6]=[C:2]([NH:1][C:20](=[O:21])[OH:22])[S:3][C:4]=2[CH:10]=[CH:9][CH:8]=1
Reactant: O=C([O-])Cl
Reactant: COc1cccc2sc(N)nc12
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1cccc2sc(NC(=O)O)nc12
Reaction time: 0.17 h

Procedure:
2-Amino-4-methoxybenzothiazol (23.6 g, 131 mmol) and pyridine (12.6 ml, 157 mmol) in dichloromethane (230 ml) are slowly treated with methyll chloroformate (10.6 ml, 137 mmol) at 0° C. After 10 minutes, further methyll chloroformate (1.0 ml, 13 mmol) and pyridine (1.0 ml, 12 mmol) are added. After 10 minutes, the mixture is poured into 200 ml 1M aqueous hydrochloric acid, the organic layer is separated, diluted with dichloromethane (250 ml) and washed with brine (50 ml). The organic phase is dried and the solvent evaporated in vacuo. 31.0 g (99.4%) white solid. MS: m/e=238 (M+H+).
Reaction SMILES: [CH3:1][C:2]([C:6]1[CH:11]=[C:10]([CH2:12][N:13]2[CH:17]=[N:16][CH:15]=[N:14]2)[CH:9]=[C:8]([CH2:18][S:19][CH3:20])[CH:7]=1)([CH3:5])[C:3]#[N:4].I([O-])(=O)(=O)=[O:22].[Na+]>CO.O1CCCC1.O>[CH3:5][C:2]([C:6]1[CH:11]=[C:10]([CH2:12][N:13]2[CH:17]=[N:16][CH:15]=[N:14]2)[CH:9]=[C:8]([CH2:18][S:19]([CH3:20])=[O:22])[CH:7]=1)([CH3:1])[C:3]#[N:4]
Reactant: CSCc1cc(Cn2cncn2)cc(C(C)(C)C#N)c1
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CS(=O)Cc1cc(Cn2cncn2)cc(C(C)(C)C#N)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of the product of Example 30 (0.16 g) in methanol (0.5 ml) and tetrahydrofuran (5 ml) was stirred while a solution of sodium periodate (0.15 g) in water (0.5 ml) was added, and was then stirred at room temperature for a further 18 h. Water (5 ml) was added and the mixture was extracted six times with dichloromethane. The extracts were combined, dried and evaporated to dryness, and the residue was purified by flash column chromatography, eluting with methanol:ethyl acetate (1:9 by volume) to give 2-methyl-2-[3-methylsulphinylmethyl-5-(1H-1,2,4-triazol-1-ylmethyl)phenyl]-propiononitrile. Nmr in deuteriochloroform; δ 8.16(1H,s), 8.0(1H,s), 7.38(1H,m), 7.27(1H,m), 7.15(1H,m), 5.4(2H,s), 3.98(1H,d), 3.88(1H,d), 2.5(3H,s), 1.72(6H,s).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([CH2:15][C:16]([OH:18])=[O:17])[CH2:11][C:12]([OH:14])=O)=[CH:9][C:4]=2[O:3][CH2:2]1>C(OC(=O)C)(=O)C>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]3[CH2:11][C:12](=[O:14])[O:18][C:16](=[O:17])[CH2:15]3)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: O=C(O)CC(CC(=O)O)c1ccc2c(c1)OCO2
Solvent: CC(=O)OC(C)=O
Product: O=C1CC(c2ccc3c(c2)OCO3)CC(=O)O1
Temperature: 25 °C
Yield: 70.3 %

Procedure:
3-(1,3-benzodioxol-5-yl)pentanedioic acid (2 g, 7.9 mmoles) was suspended in acetic anhydride (50 ml) and refluxed for two hours. The reaction mixture was allowed to cool to room temperature and the solvent was removed under reduced pressure. The residue was triturated with ether to give the product (1.3 g, 70%). 1H NMR (DMSO-d6) δ 6.91 (m, 1H), 6.89 (m, 1H), 6.72 (m, 1H), 6.01 (s, 2H), 3.53-3.41 (m, 1H), 3.07-2.89 (m, 4H).
Reaction SMILES: [CH2:1]([C:3](CO)(C)[C:4]([OH:6])=[O:5])O.O=C=[N:12]C1CC(C)(C)CC(C)(CN=C=O)C1.[C:26]([O:30][CH2:31][CH2:32]O)(=[O:29])C=C>>[C:4]([OH:6])(=[O:5])[CH:3]=[CH2:1].[NH2:12][C:26]([O:30][CH2:31][CH3:32])=[O:29]
Reactant: C=CC(=O)OCCO
Reactant: CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1
Reactant: CC(CO)(CO)C(=O)O
Product: C=CC(=O)O
Product: CCOC(N)=O

Procedure:
In the same manner as in Preparation Example 1 <PUA-1>, except that 2490 g (3 mol) of polycaprolactonediol (PLACCEL208, manufactured by DAICEL CHEMICAL INDUSTRIES, LTD.) having a molecular weight of 830 as the polymer polyol, 402 g (3 mol) of dimethylolpropionic acid as the dihydroxyl compound having a carboxyl group, 1554 g (7 mol) of isophorone diisocyanate as the polyisocyanate and 238 g (2.05 mol) of 2-hydroxyethyl acrylate as the (meth)acrylate having a hydroxyl group were respectively used, a urethane acrylate was synthesized.
Reaction SMILES: Cl[C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[F-:12].[K+]>>[Cl:8][C:7]1[C:2]([F:12])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1cccc(Cl)c1Cl
Reactant: [F-]
Agent: [K+]
Product: O=[N+]([O-])c1cccc(Cl)c1F
Temperature: 150 °C
Reaction time: 2 h

Procedure:
57.6 g (0.3 mol) of 2,3-dichloronitrobenzene and 13.9 g (0.24 mol) of potassium fluoride were introduced into a 100 ml flange flask and fitted with a reflux condenser and blade stirrer and stirred at 150° C. for 2 hours (no reaction). The reaction suspension was heated to 190° C. and stirred for a further 4 hours at this temperature. Amount of 3-chloro-2-fluoronitrobenzene formed: after 2 hours: 1 GC area-%. after 8 hours: 8 GC area-%.
Reaction SMILES: [CH2:1]=[CH:2][CH:3]([OH:10])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[Na+].[Br-].[OH2:13].[CH3:14]O>>[O:10]1[CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])[CH:2]1[CH2:1][O:13][CH3:14]
Reactant: C=CC(O)CCCCCC
Reactant: CO
Reactant: O
Agent: [Br-]
Agent: [Na+]
Product: CCCCCCC1OC1COC

Procedure:
Electrolyte: 300 g (2.113 moles) of non-1-en-3-ol, 60 g of NaBr, 60 g of water, and 2,580 g of methanol
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:10])[CH:5]=[CH:6][C:7]=1[Cl:8].[C:17](Cl)(Cl)=[S:18]>O1CCOCC1>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:10])=[CH:3][C:2]=1[N:1]=[C:17]=[S:18]
Reactant: Nc1cc(C(=O)c2ccccc2)ccc1Cl
Reactant: S=C(Cl)Cl
Solvent: C1COCCO1
Product: O=C(c1ccccc1)c1ccc(Cl)c(N=C=S)c1
Yield: 85 %

Procedure:
A mixture of 17 parts of (3-amino-4-chlorophenyl)phenylmethanone, 9.5 parts of carbonothioic dichloride and 200 parts of 1,4-dioxane is stirred and refluxed for 15 minutes. The reaction mixture is evaporated and the oily residue is crystallized from 2,2'-oxybispropane. The product is filtered off and dried, yielding 17 parts (85%) of (4-chloro-3-isothiocyanatophenyl)phenylmethanone; mp. 96.7° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][NH:6][C:7](=[O:15])[CH2:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11].[CH2:20]([O:22][C:23](=[O:34])[C:24]1[CH:29]=[CH:28][C:27](F)=[C:26]([N+:31]([O-:33])=[O:32])[CH:25]=1)[CH3:21].C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[F:19])[CH2:5][NH:6][C:7](=[O:15])[CH:8]([C:27]1[CH:28]=[CH:29][C:24]([C:23]([O:22][CH2:20][CH3:21])=[O:34])=[CH:25][C:26]=1[N+:31]([O-:33])=[O:32])[C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11]
Reactant: CCOC(=O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: CC(C)(C)C(=O)CC(=O)NCc1ccc(F)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: CCOC(=O)c1ccc(C(C(=O)NCc2ccc(F)c(F)c2)C(=O)C(C)(C)C)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of N-(3,4-difluorobenzyl)-4,4-dimethyl-3-oxopentanamide (Compound 112, 126 mg, 0.47 mmol) and ethyl4-fluoro-3-nitrobenzoate (Compound 113, 100 mg, 0.47 mmol) in DMSO (1 ml) was added K2CO3 (130 mg, 0.94 mmol). The mixture was stirred at room temperature for 16 h, diluted with EtOAc, washed with 1 M HCl, H2O, and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→30% EtOAc-hexanes) to yield the title compound as a yellow solid.
Reaction SMILES: [NH2:1][C@H:2]([C@H:10]([OH:22])[C@H:11]([OH:21])[C@@H:12]([NH2:20])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:23]([O:27][C:28](O[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[O:29])([CH3:26])([CH3:25])[CH3:24]>ClCCl>[NH2:1][C@@H:2]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C@@H:10]([OH:22])[C@@H:11]([OH:21])[C@@H:12]([NH:20][C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:29])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[C:23]([O:27][C:28]([NH:1][CH:2]([CH:10]([OH:22])[CH:11]([OH:21])[CH:12]([NH:20][C:31]([O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:32])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Reactant: N[C@@H](Cc1ccccc1)[C@H](O)[C@H](O)[C@@H](N)Cc1ccccc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC(Cc1ccccc1)C(O)C(O)C(Cc1ccccc1)NC(=O)OC(C)(C)C
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@H](O)[C@H](O)[C@@H](N)Cc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 56 %
Yield: 20 %

Procedure:
A solution of 200 mg (0.67 mmol) of (2S,3S,4R,5S)-2,5-diamino-3,4-dihydroxy1,6-diphenylhexane in 10 ml of dichloromethane was treated with 174 mg (0.8 mmol) of di-t-butyldicarbonate. After being allowed to stir overnight at ambient temperature, the solution was concentrated, and the residue was purified by silica gel chromatography using 10% methanol in chloroform to provide 180 mg (56%) of the desired compound along with 80 mg (20%) of the resultant compound of Example 206.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C[Al](C)C.[S:16]1[CH:20]=[CH:19][CH:18]=[C:17]1[C:21]#[N:22]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[CH3:1][S:2]([C:5]1[CH:11]=[CH:10][C:8]([NH:9][C:21]([C:17]2[S:16][CH:20]=[CH:19][CH:18]=2)=[NH:22])=[CH:7][CH:6]=1)(=[O:3])=[O:4]
Reactant: CS(=O)(=O)c1ccc(N)cc1
Reactant: N#Cc1cccs1
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: CS(=O)(=O)c1ccc(NC(=N)c2cccs2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a suspension of 4-(methylsulfonyl)aniline (10.4 g, 61.1 mmol) in toluene (400 ml) at 0° C., trimethylaluminum (2M solution in toluene, 46.8 ml, 91.6 mmol) was added over 15 minutes. The reaction mixture was warmed to room temperature and stirred for 2 hours. A solution of 2-thiophenecarbonitrile (10.0 g, 91.6 mmol) in toluene (200 ml) was added over 10 minutes and the mixture was heated to 80°-85° C. After 16 hours, the reaction mixture was cooled to room temperature and poured over a slurry of silica gel in chloroform. After filtration, the residue was washed with a mixture of methylene chloride/methanol and later with methanol. The combined filtrates were concentrated and the resulting yellow solid was stirred with ethyl acetate and filtered. The pale yellow solid (9.8 g, 57%) was used in the next reaction without further purification: m.p. (DSC) 182° C. Anal. Calc'd. for C12H12N2S2O2 : C, 51.41, H, 4.31, N, 9.99, S, 22.87 Found C, 51.02, H, 4.37, N, 9.80, S, 22.93,
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13](=[O:29])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.[F:38][C:39]1[C:44]([F:45])=[C:43]([F:46])[CH:42]=[CH:41][C:40]=1B(O)O.[F-].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)=[CH:18][CH:19]=1)=[O:29])=[C:8]([C:42]1[CH:41]=[CH:40][C:39]([F:38])=[C:44]([F:45])[C:43]=1[F:46])[CH:7]=[CH:6]2
Reactant: OB(O)c1ccc(F)c(F)c1F
Reactant: COc1ccc2c(C(=O)c3ccc(OCCN4CCCCC4)cc3)c(OS(=O)(=O)C(F)(F)F)ccc2c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cs+]
Agent: [F-]
Solvent: CC#N
Product: COc1ccc2c(C(=O)c3ccc(OCCN4CCCCC4)cc3)c(-c3ccc(F)c(F)c3F)ccc2c1
Temperature: 80 °C
Yield: 42.3 %

Procedure:
Charge a flask with trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (2.13 g, 4.0 mmol), 2,3,4-trifluorophenyl boronic acid (1.0 g, 5.7 mmol), trans-dichlorobis(triphenylphosphine)palladium II, (561 mg, 0.8 mmol) and cesium fluoride (5.5 g, 36 mmol) and add 50 mL of acetonitrile. Heat the mixture at 80° C. for 4 hours. Cool and filter the mixture and purify on an SOX column, eluting with 2N ammonia/ethanol. Purify further on a silica column eluting with 2% 2N ammonia/methanol/methylene chloride to give 880 mg (43%) of the title compound: 1H-NMR (CD3OD, 400 MHz) δ 7.93 (d, J=8.8 Hz, 1H); 7.50 (d, J=8.4 Hz, 3H); 7.39 (d, J=8.8 Hz, 1H); 7.35 (d, J=2.4 Hz, 1H); 7.07 (dd, J=9.2, 2.8 Hz, 1H); 6.96-6.87 (m, 2H); 6.80 (d, J=9.6 Hz, 2H); 4.10-4.07 (t, 2H); 3.91 (s, 3H); 2.72-2.69 (t, 2H); 2.48-2.48 (m, 4H); 1.61-1.55 (m, 4H); 1.46-1.43 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8]C(NCCCl)C#N)=[CH:4][CH:3]=1.[CH2:16]([S:18][C:19]1[NH:20][CH:21]=[CH:22][C:23]=1[N+:24]([O-:26])=[O:25])[CH3:17].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:20]([CH2:21][CH2:22][C:22]2[C:23]([N+:24]([O-:26])=[O:25])=[C:19]([S:18][CH2:16][CH3:17])[NH:20][CH:21]=2)[CH2:19][C:23]#[N:24])=[CH:4][CH:3]=1
Reactant: CCSc1[nH]ccc1[N+](=O)[O-]
Reactant: N#CC(Cc1ccc(Cl)nc1)NCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCSc1[nH]cc(CCN(CC#N)Cc2ccc(Cl)nc2)c1[N+](=O)[O-]

Procedure:
This compound was prepared in a manner analogous to that set forth in Step G of Example 1, using 0.17 gram (0.0007 mole) of 2-{[(6-chloro(3-pyridyl)methyl] (2-chloroethylamino}ethanenitrile (prepared in Steps A and B of the present Example), 0.10 gram (0.00064 mole) of 2-ethylthio-3-nitropyrrole and 0.22 gram (0.0016 mole) of potassium carbonate in about 15 mL of DMF. The crude product was purified with column chromatography on silica gel. Elution was accomplished using 50% hexane in diethyl ether and 100% diethyl ether as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.10 gram of Compound I. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: C([O-])(=O)C.[CH2:5]([Sn+:9]([CH2:14][CH2:15][CH2:16][CH3:17])[CH2:10][CH2:11][CH2:12][CH3:13])[CH2:6][CH2:7][CH3:8].[P:18]([O-:25])([O:22]CC)[O:19][CH2:20][CH3:21]>C(OCC)(=O)C>[CH2:20]([O:19][P:18]([O-:25])[O-:22])[CH3:21].[CH2:14]([Sn+2:9]([CH2:5][CH2:6][CH2:7][CH3:8])[CH2:10][CH2:11][CH2:12][CH3:13])[CH2:15][CH2:16][CH3:17]
Reactant: CCCC[Sn+](CCCC)CCCC
Reactant: CCOP([O-])OCC
Agent: CC(=O)[O-]
Solvent: CCOC(C)=O
Product: CCCC[Sn+2](CCCC)CCCC
Product: CCOP([O-])[O-]
Yield: 101 %

Procedure:
In a 500 ml four-neck round-bottom flask having a thermometer, stirrer, standard taper glass stopper, stillhead with condenser, cooled distillate receiver and cold trap, 116.4 g of tributyltin acetate and 92 g of diethyl phosphite are heated with stirring to about 150° with ethyl acetate being distilled off. After a reaction time of 6 hours, of which one hour is under vacuum, ca. 5 mm Hg, the excess dimethyl phosphite is distilled off and 134 g of tributyltin ethyl phosphite are obtained.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[C:3]1[CH:8]=[CH:7][C:6]([N:9]=[C:10]=[S:11])=[CH:5][CH:4]=1.[CH3:13][C:14]([CH3:18])([CH3:17])[CH2:15][NH2:16]>C(OCC)C>[CH3:1][N:2]([CH3:12])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([NH:16][CH2:15][C:14]([CH3:18])([CH3:17])[CH3:13])=[S:11])=[CH:5][CH:4]=1
Reactant: CC(C)(C)CN
Reactant: CN(C)c1ccc(N=C=S)cc1
Solvent: CCOCC
Product: CN(C)c1ccc(NC(=S)NCC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 85.9 %

Procedure:
To a solution of 4-dimethylaminophenyl isothiocyanate (4.5 g, 25 mmol) in diethyl ether (100 mL) at room temperature was added a solution of 2,2-dimethyl-1-propanamine (2.94 mL, 25 mmol) and the reaction was stirred at room temperature for 3 hours. The precipitated solid was collected by filtration and dried to afford 5.7 g (85%) of N-[4-(dimethylamino)phenyl]-N′-(2,2-dimethylpropyl)-thiourea, as a white solid: mp 174–176° C.; 1H NMR (DMSO-d6): δ 9.17 (br s, 1H), 7.13 (d, 2H), 7.10 (br s, 1H), 6.68 (d, 2H), 3.33 (d, 2H), 2.86 (s, 6H), and 0.87 ppm (s, 9H); IR (KBr) 3400, 3160, 1600, 1550 cm−1; MS (m/z) 265 (M+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]([CH3:13])([CH2:11][CH3:12])[C:9]#[N:10])[CH:5]=[CH:6][CH:7]=1.[AlH3].C1(C)C=CC=CC=1>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:8]([CH3:13])([CH2:11][CH3:12])[CH2:9][NH2:10])[CH:5]=[CH:6][CH:7]=1
Reactant: CCC(C)(C#N)c1cccc(Br)c1
Agent: [AlH3]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCC(C)(CN)c1cccc(Br)c1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 66.7 %

Procedure:
A solution of 2-(3-bromophenyl)-2-methylbutanenitrile (1678.5 mg, 7.049 mmol) in dry THF (28 mL) was cooled in an ice-bath. AlH3:(Me)2EtN complex, 0.5M in PhMe (28.20 mL of 0.5 M, 14.10 mmol) was added slowly dropwise and the resultant solution stirred at 0° C. for 30 mins. The mixture was allowed to warm to RT and stirred for 4.5 hours. The reaction was carefully quenched by dropwise addition of 1:1 THF:water (˜30 mL). The resulting suspension was stirred vigorously and filtered through a pad of celite. The collected solid was partitioned between EtOAc and brine and the aqueous layer further extracted with EtOAc (3×50 mL) and the combined organics dried over Na2SO4, filtered and concentrated under reduced pressure to give a light brown oil. The residue was purified on silica gel by flash column chromatography (5% MeOH in DCM, loaded in DCM, ˜200 mL silica) to give the product as a yellow oil (1137.8 mg, 67% Yield).