Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN(C)C=O.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=2)=[C:9]([Cl:30])[CH:8]=1.[CH3:31][C:32]1[C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][N:35]=[C:34]([O:47][CH2:48][C:49]2([C:52]([O:54][CH3:55])=[O:53])[CH2:51][CH2:50]2)[CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C(OCC)(=O)C>[Cl:30][C:9]1[CH:8]=[C:7]([C:37]2[C:32]([CH3:31])=[CH:33][C:34]([O:47][CH2:48][C:49]3([C:52]([O:54][CH3:55])=[O:53])[CH2:50][CH2:51]3)=[N:35][CH:36]=2)[CH:12]=[CH:11][C:10]=1[C:13]1[N:14]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=1
Reactant: C[Si](C)(C)CCOCn1cc(C(F)(F)F)nc1-c1ccc(Br)cc1Cl
Reactant: COC(=O)C1(COc2cc(C)c(B3OC(C)(C)C(C)(C)O3)cn2)CC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)C1(COc2cc(C)c(-c3ccc(-c4nc(C(F)(F)F)cn4COCC[Si](C)(C)C)c(Cl)c3)cn2)CC1
Temperature: 65 °C
Reaction time: 2 h
Yield: 82.4 %

Procedure:
N,N-dimethylformamide (11 mL) was added to 2-(4-bromo-2-chlorophenyl)-4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole (220 mg), methyl 1-({[4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]oxy}-methyl)cyclopropanecarboxylate (201 mg), and palladium chloride (dppf) methylene chloride complex (39 mg), and after adding 2N aqueous sodium carbonate solution (0.72 mL) to the mixture, the atmosphere was replaced with nitrogen and the mixture was stirred at 65° C. for 2 hours. To the reaction mixture were added ethyl acetate and water to extract the objective compound, and the organic layer was washed with a saturated brine, and dried over anhydrous sodium sulfate. After concentrating the mixture under reduced pressure, the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=95:5 to 80:20) to obtain methyl 1-{[(5-{3-chloro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]methyl}cyclopropanecarboxylate (237 mg).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:12]2C(=O)OC(C)(C)[O:14][C:13]2=[O:21])[C:9]#[C:10][CH3:11])=[CH:4][CH:3]=1.Cl>N1C=CC=CC=1.O>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:9]#[C:10][CH3:11])[CH2:12][C:13]([OH:21])=[O:14])=[CH:6][CH:7]=1
Reactant: CC#CC(c1ccc(O)cc1)C1C(=O)OC(C)(C)OC1=O
Agent: Cl
Solvent: O
Solvent: c1ccncc1
Product: CC#CC(CC(=O)O)c1ccc(O)cc1
Yield: 95.2 %

Procedure:
A solution of 5-[1-(4-hydroxyphenyl)but-2-ynyl]-2,2-dimethyl-1,3-dioxane-4,6-dione (20 g, 69.44 mmol) in pyridine-water (5:1, 390 mL) is heated at reflux for 16 hours and after cooling is acidified to pH ˜2 with 5 N HCl and extracted with EtOAc (2×300 mL). The combined extracts are washed with saturated brine, dried over MgSO4, filtered, and concentrated to give an off-white solid (13.5 g, 96%). ESI/MS m/z 203 (M−H)−.
Reaction SMILES: [OH-].[K+].N.[Br:4][C:5]1[CH:6]=[CH:7][C:8]2[NH:9][C:10]3[C:15]([C:16]=2[CH:17]=1)=[CH:14][CH:13]=[CH:12][CH:11]=3.[NH2-].[Na+].Br[CH2:21][C:22]#[CH:23].[K+].[Br-]>>[CH2:23]([N:9]1[C:8]2[CH:7]=[CH:6][C:5]([Br:4])=[CH:17][C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:22]#[CH:21]
Reactant: C#CCBr
Reactant: Brc1ccc2[nH]c3ccccc3c2c1
Agent: N
Agent: [Br-]
Agent: [K+]
Product: C#CCn1c2ccccc2c2cc(Br)ccc21
Temperature: -33 °C
Reaction time: 3 h
Yield: 95 %

Procedure:
A 500 ml, three-necked, round bottom flask was fitted with mechanical stirrers, thermometer, Dry Ice/acetone reflex condenser (with KOH drying tube) and addition funnel. To the flask was added 210 ml of liquid ammonia and 8.7 g (0.035 mole) of 3-bromocarbazole (from Example 16A). To this mixture was added 1.52 g (0.039 mole) of sodium amide at -33° C. The resulting mixture was stirred mechanically at -33° C for 3 hr. The mixture was then cooled to -55° C and 5.9 g (0.049 mole) of 3-bromo-1-propyne was added dropwise over a period of 20 min. After stirring at -55+ C for an additional 5 hr, the ammonia was allowed to evaporate overnight. The residue was extracted three times with 300 ml portions of benzene. Concentration of the combined benzene extractants gave 9.5 g (95% yield) of light yellow powder, m.p. 142°-149° C. Recrystallization from methanol gave colorless needle crystals, m.p. 155°-157° C. I.R. (KBr pellet) in cm-1 : 3300 (C≡CH), 3070 (Ar H), 2940 (CH) , 2140 (C≡C), 1630 + 1600 (C=C), 1455 + 1330 (CN), 800 + 740 + 720 (Ar), 680 + 660 (C≡CH).
Reaction SMILES: [CH3:1][NH:2][CH:3]1[CH2:16][C:15]2[C:6]([CH3:25])([CH:7]3[CH:12]([CH2:13][CH:14]=2)[CH:11]2[CH2:17][CH2:18][CH:19]4[CH:20]([CH3:24])[N:21]([CH3:23])[CH2:22][C:10]24[CH2:9][CH2:8]3)[CH2:5][CH2:4]1.[CH3:26][O:27][CH:28]([CH2:32][CH2:33][CH2:34][CH3:35])[C:29](O)=[O:30].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>ClCCl>[CH3:1][N:2]([CH:3]1[CH2:16][C:15]2[C:6]([CH3:25])([CH:7]3[CH:12]([CH2:13][CH:14]=2)[CH:11]2[CH2:17][CH2:18][CH:19]4[CH:20]([CH3:24])[N:21]([CH3:23])[CH2:22][C:10]24[CH2:9][CH2:8]3)[CH2:5][CH2:4]1)[C:29](=[O:30])[CH:28]([O:27][CH3:26])[CH2:32][CH2:33][CH2:34][CH3:35]
Reactant: CCCCC(OC)C(=O)O
Reactant: CNC1CCC2(C)C(=CCC3C2CCC24CN(C)C(C)C2CCC34)C1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: CCCCC(OC)C(=O)N(C)C1CCC2(C)C(=CCC3C2CCC24CN(C)C(C)C2CCC34)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.7 %

Procedure:
A mixture of compound 7B (30 mg, 0.088 mmol), 2-methoxy caproic acid (20 mg, 0.137 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodimide hydrochloride (34 mg, 0.177 mmol), 1-hydroxybenzotriazole (24 mg, 0.177 mmol) and dichloromethane (1 mL) was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and the residue was dissolved in minimum amount of dichloromethane and purified on silica gel column, which was eluted with 0.3% ammonium hydroxide and 3% methanol in dichloromethane to give the desired product (38 mg, 92% yield).
Reaction SMILES: [NH2:1][CH2:2][C:3]([OH:5])=[O:4].[N+:6]([C:9]1[CH:19]=[CH:18][C:12]([CH2:13][O:14][C:15](Cl)=[O:16])=[CH:11][CH:10]=1)([O-:8])=[O:7]>[OH-].[Na+].CCOCC>[N+:6]([C:9]1[CH:10]=[CH:11][C:12]([CH2:13][O:14][C:15]([NH:1][CH2:2][C:3]([OH:5])=[O:4])=[O:16])=[CH:18][CH:19]=1)([O-:8])=[O:7]
Reactant: O=C(Cl)OCc1ccc([N+](=O)[O-])cc1
Reactant: NCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Product: O=C(O)CNC(=O)OCc1ccc([N+](=O)[O-])cc1
Reaction time: 2 h

Procedure:
A 3.75 g portion of glycine was dissolved in 25 ml of 2N sodium hydroxide aqueous solution, and to the resulting solution cooled on an ice bath were simultaneously added in dropwise 10.77 g of p-nitrobenzyloxycarbonyl chloride dissolved in ether and 12.5 ml of 4N sodium hydroxide aqueous solution. After stirring at the same temperature for 2 hours, the reaction solution was washed with ether, the resulting aqueous layer was adjusted to acidic with concentrated hydrochloric acid, and the thus precipitated solid material was collected by filtration, washed with water and then dried to yield 11.98 g of N-(p-nitrobenzyloxycarbonyl)glycine as a white solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:14]([C:15]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[C:16]4[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]4)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:4][CH:3]=1.[CH:28]1[C:40]2[N:39]([C:41]3[CH:46]=[CH:45][C:44]([C:47]4[CH:48]=[CH:49][C:50]5[NH:51][C:52]6[C:57]([C:58]=5[CH:59]=4)=[CH:56][CH:55]=[CH:54][CH:53]=6)=[CH:43][CH:42]=3)[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]=2[CH:31]=[CH:30][CH:29]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>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].C1(C)C=CC=CC=1.CCCCCC>[CH:28]1[C:40]2[N:39]([C:41]3[CH:46]=[CH:45][C:44]([C:47]4[CH:48]=[CH:49][C:50]5[N:51]([C:2]6[CH:3]=[CH:4][C:5]([C:8]7[C:21]8[C:16]([C:15]([C:22]9[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=9)=[C:14]9[C:9]=7[CH:10]=[CH:11][CH:12]=[CH:13]9)=[CH:17][CH:18]=[CH:19][CH:20]=8)=[CH:6][CH:7]=6)[C:52]6[C:57]([C:58]=5[CH:59]=4)=[CH:56][CH:55]=[CH:54][CH:53]=6)=[CH:43][CH:42]=3)[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]=2[CH:31]=[CH:30][CH:29]=1
Reactant: Brc1ccc(-c2c3ccccc3c(-c3ccccc3)c3ccccc23)cc1
Reactant: c1ccc2c(c1)[nH]c1ccc(-c3ccc(-n4c5ccccc5c5ccccc54)cc3)cc12
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: CC(C)(C)[O-]
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: c1ccc(-c2c3ccccc3c(-c3ccc(-n4c5ccccc5c5cc(-c6ccc(-n7c8ccccc8c8ccccc87)cc6)ccc54)cc3)c3ccccc23)cc1
Temperature: 25 °C
Yield: 78.4 %

Procedure:
1.8 g (4.5 mmol) of 9-(4-bromophenyl)-10-phenylanthracene, 1.8 g (4.5 mmol) of 3-[4-(9H-carbazol-9-yl)phenyl]-9H-carbazole (CPC), and 1.1 g (10 mmol) of sodium tert-butoxide were put into a 200 mL three-neck flask. The air in the flask was replaced with nitrogen. To the mixture were added 25 mL of toluene and 0.10 mL of tri(tert-butyl)phosphine (a 10 wt % hexane solution). This mixture was stirred to be degassed while the pressure was reduced. After the degassing, 58 mg (0.10 mmol) of bis(dibenzylideneacetone)palladium(0) was added to the mixture. This mixture was refluxed and then cooled to room temperature. Then, to the mixture was added about 50 mL of toluene. The mixture was subjected to suction filtration through Florisil (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 540-00135), celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855), and alumina. The obtained filtrate was condensed to give a light yellow solid. This solid was recrystallized with toluene/hexane to give 2.6 g of a light yellow powdered solid, which was the object of the synthesis, at a yield of 81%. A synthesis scheme of Step 4 is shown in (f-4) given below.
Reaction SMILES: C([CH:4]1[C:9]2[NH:10][C:11]3[CH:12]=[N:13][C:14]4[C:19]([C:20]=3[C:8]=2[CH2:7][NH:6][CH2:5]1)=[CH:18][CH:17]=[C:16]([Cl:21])[CH:15]=4)(=O)C>Cl>[Cl:21][C:16]1[CH:15]=[C:14]2[C:19]([C:20]3[C:8]4[CH2:7][NH:6][CH2:5][CH2:4][C:9]=4[NH:10][C:11]=3[CH:12]=[N:13]2)=[CH:18][CH:17]=1
Reactant: CC(=O)C1CNCc2c1[nH]c1cnc3cc(Cl)ccc3c21
Agent: Cl
Product: Clc1ccc2c(c1)ncc1[nH]c3c(c12)CNCC3
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture prepared from 27 g of 8-acetyl-3-chloro-7,8,9,10-tetrahydro-11H-pyrido[3',4':4,5]pyrrolo[2,3-c]quinoline and 200 ml of concentrated hydrochloric acid was heated at reflux for 1 hour, whereupon a solid precipitated. The mixture was stirred overnight at room temperature, and the solid was filtrated and dissolved in 200 ml of water. This solution was made alkaline with 25% sodium hydroxide solution, and the solid-form free base was filtrated and washed with ethanol. The yield was 17 g, mp=285° C. (dec).
Reaction SMILES: [CH:1]1([NH:6][NH2:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(O[CH:11]=[C:12]([C:15]#[N:16])[C:13]#[N:14])C>CO>[NH2:16][C:15]1[N:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[N:7]=[CH:11][C:12]=1[C:13]#[N:14]
Reactant: CCOC=C(C#N)C#N
Reactant: NNC1CCCC1
Solvent: CO
Product: N#Cc1cnn(C2CCCC2)c1N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Cyclopentylhydrazine (6.5 g, 64.9 mmol) is slowly added to a solution of ethoxymethylenemalononitrile (7.93 g, 64.9 mmol) in 100 ml of methanol at room temperature under argon, subsequently heated under reflux for 3 h and then stirred at room temperature overnight. The solvent is stripped off in a rotary evaporator and the residue is stirred with diethyl ether. The solid is filtered off with suction, washed with diethyl ether and dried under high vacuum.
Reaction SMILES: [CH3:1][N:2]([CH3:28])[C:3]([C:5]1[N+:10]([O-])=[CH:9][C:8]([O:12][C:13]2[C:18]3[CH:19]=[C:20]([CH3:22])[O:21][C:17]=3[CH:16]=[C:15]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:14]=2)=[CH:7][CH:6]=1)=[O:4]>C(O)(=O)C.[Fe]>[CH3:28][N:2]([CH3:1])[C:3]([C:5]1[N:10]=[CH:9][C:8]([O:12][C:13]2[C:18]3[CH:19]=[C:20]([CH3:22])[O:21][C:17]=3[CH:16]=[C:15]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:14]=2)=[CH:7][CH:6]=1)=[O:4]
Reactant: CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)[n+]([O-])c2)c2cc(C)oc2c1
Agent: [Fe]
Solvent: CC(=O)O
Product: CCOC(=O)c1cc(Oc2ccc(C(=O)N(C)C)nc2)c2cc(C)oc2c1
Temperature: 25 °C
Yield: 80.2 %

Procedure:
To a stirred solution of ethyl 4-({6-[(dimethylamino)carbonyl]-1-oxidopyridin-3-yl}oxy)-2-methyl-1-benzofuran-6-carboxylate (176 mg, 0.457 mmol) in 15 mL of acetic acid, was added powdered Fe while keeping the temperature at 70° C. for 2 hrs. LC-MS showed that the reaction was complete. The reaction was cooled to room temperature, and the insoluble material was filtered. The mother liquor was diluted with EtOAc, washed with NaHCO3, brine, and dried over Na2SO4, and concentrated. The crude product was introduced into a silica gel column and eluted with MeOH/CHCl3 (2/98 to 5/95) to provide the product (135 mg, 85% yield) as colorless oil. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.40 (t, J=7.16 Hz, 3 H) 2.47 (s, 3 H) 3.15 (d, 6 H) 4.39 (q, J=7.03 Hz, 2 H) 6.25 (s, 1 H) 7.30 (d, J=2.45 Hz, 1 H) 7.55-7.64 (m, 1 H) 7.64-7.76 (m, 1 H) 8.00 (s, 1 H) 8.38 (s, 1 H); LC-MS (ESI)+m/z=369.00 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C@H:7]2[CH2:12][CH2:11][NH:10][CH2:9][C@H:8]2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C=O.[OH-].[Na+].[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29]>CCOCC.C(O)C.C(O)=O>[C:25]([OH:32])(=[O:31])/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29].[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C@H:7]2[CH2:12][CH2:11][N:10]([CH3:25])[CH2:9][C@H:8]2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:19][CH:20]=1
Reactant: Brc1ccc(O[C@H]2CCNC[C@H]2c2ccccc2)cc1
Agent: C=O
Agent: O=C(O)/C=C/C(=O)O
Agent: [Na+]
Solvent: CCOCC
Solvent: O=CO
Solvent: CCO
Product: CN1CC[C@H](Oc2ccc(Br)cc2)[C@H](c2ccccc2)C1

Procedure:
A mixture of 2.4 g of cis-4-(4-bromophenoxy)-3-phenylpiperidine, 7.2 ml of 100% formic acid and 0.81 ml of 37% aqueous formaldehyde solution is refluxed for one hour under nitrogen, cooled and made basic with 35 ml of 10% aqueous sodium hydroxide solution. The mixture is extracted with ether (2×50 ml), the ether extracts are washed with saturated sodium chloride solution, dried overnight over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil. The oil is dissolved in 50 ml of ether and treated dropwise with stirring with a solution of 0.89 g of fumaric acid in a mixture of 75 ml of ether and 15 ml of absolute ethanol. The colorless, fine crystals which precipitate are filtered, washed with ether and dried to afford solid product, mp 172° C. dec.
Reaction SMILES: Br[C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]([C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:16])=[O:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[CH3:25][Si:26]([C:29]#[CH:30])([CH3:28])[CH3:27].Cl>C(N(CC)CC)C.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>[CH3:25][Si:26]([C:29]#[C:30][C:2]1[CH:24]=[CH:23][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]([C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:16])=[O:14])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1)([CH3:28])[CH3:27]
Reactant: O=C(C(=O)c1ccc(Oc2ccc(Br)cc2)cc1)c1ccccc1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1ccc(Oc2ccc(C(=O)C(=O)c3ccccc3)cc2)cc1
Yield: 100.4 %

Procedure:
4-(4-Bromophenoxy)benzil (3.81 g, 0.01 mole), trimethylsilylacetylene (1.96 g, 0.02 mole), and dichlorobis(triphenylphosphine)palladium (0.30 g) in triethylamine (20 ml) were placed under a nitrogen atmosphere in a sealed flask and heated at 66°-68° C. for four hours. The cooled brown reaction mixture was poured into cold dilute hydrochloric acid to yield a brown oil which was extracted with methylene chloride. The methylene chloride solution was washed with dilute aqueous hydrochloric acid and water, dried over magnesium sulfate, and concentrated on a rotary evaporator to yield a brown gum (4.0 g). The gum was extracted with boiling cyclohexane (100 ml) (small amount remained insoluble) and the solution treated with charcoal, filtered, and concentrated to yield 4-[(4-[trimethylsilyl)ethynyl]phenoxy]benzil as an orange gum (3.4 g, 85% yield). MS, no M+, major fragment m/e 293 [+CO--C6H4 --O--C6H4 --C≡C--Si(CH3)3 ].
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:40])[CH2:5][N:6]([C:30]([S:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])[CH2:7][P:8]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=1)([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=1)=[O:9])[CH3:2].ClC1C=CC=C(C(OO)=[O:49])C=1>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:40])[CH2:5][N:6]([C:30]([S:32]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:49])=[O:31])[CH2:7][P:8]([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=1)([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=1)=[O:9])[CH3:2]
Reactant: CCOC(=O)CN(CP(=O)(Oc1cccc([N+](=O)[O-])c1)Oc1cccc([N+](=O)[O-])c1)C(=O)SCc1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CCOC(=O)CN(CP(=O)(Oc1cccc([N+](=O)[O-])c1)Oc1cccc([N+](=O)[O-])c1)C(=O)S(=O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 63.1 %

Procedure:
To a solution of ethyl-N-[(benzylthio)carbonyl]-N-[bis(3-nitrophenoxy)phosphinylmethyl]-glycinate (2.0 g.; 0.0034 mol.) dissolved in 50 ml. of methylene chloride was added metachloroperbenzoic acid (0.69 g.; 0.0034 mol.) at 0° C. The reaction mixture was stirred for 4 hours while allowed to gradually warm to 25° C., then filtered. The filtrate was washed with 5% sodium hydroxide, dried, and concentrated in vacuo to yield ethyl-N-[(benzylsulfinyl)carbonyl]-N-[bis(3-nitrophenoxy)phosphinylmethyl]-glycinate (1.3 g.) as an oil (nD25 =1.5654) having the following analysis:
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:10])=[CH:4][C:5]([Cl:9])=[C:6]([OH:8])[CH:7]=1.[CH:11]1(Br)[CH2:15][CH2:14][CH2:13][CH2:12]1.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.O.[I-].[K+]>[Cl:9][C:5]1[C:6]([O:8][CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:7][C:2]([NH2:1])=[C:3]([F:10])[CH:4]=1
Reactant: Nc1cc(O)c(Cl)cc1F
Reactant: BrC1CCCC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [I-]
Solvent: Cc1ccccc1
Solvent: O
Product: Nc1cc(OC2CCCC2)c(Cl)cc1F
Temperature: 25 °C
Yield: 81.9 %

Procedure:
A three-necked flask (2,000 cc) equipped with a mechanical stirrer was charged with 5-amino-2-chloro-4-fluorophenol (75.0 g, 0.464 mol), cyclopentyl bromide (76.3 g, 0.512 mol), tetrabutylammonium bromide (3.03 g, 9.41 mmol) and potassium iodide (776 mg, 4.67 mmol) to prepare a solution in toluene (500 mL). Subsequently, 40% sodium hydroxide in aqueous solution (500 mL) was added slowly and the mixture was stirred under heating at 80° C. (in water bath at 85°-90° C.) for 7 h. After completion of the reaction, the reaction mixture was cooled to room temperature and water (500 mL) was added, followed by extraction with toluene (400 mL×2). The organic layers were combined, washed with water (100 mL) and saturated brine (100 mL) and dried with anhydrous magnesium sulfate. After the desiccant was removed, the solvent was distilled off under vacuum to give 4-chloro-5-cyclopentyloxy-2-fluoroaniline (87.2 g, 0.380 mol; yield=81.8%).
Reaction SMILES: [C:1]1([C:13]([OH:15])=[O:14])[CH:6]=[CH:5][CH:4]=[C:3]([C:7]([OH:9])=[O:8])[C:2]=1[C:10]([OH:12])=[O:11].S(=O)(=O)(O)O.[N+:21]([O-])([O-:23])=[O:22].[K+]>O>[N+:21]([C:5]1[CH:6]=[C:1]([C:13]([OH:15])=[O:14])[C:2]([C:10]([OH:12])=[O:11])=[C:3]([C:7]([OH:9])=[O:8])[CH:4]=1)([O-:23])=[O:22]
Reactant: O=[N+]([O-])[O-]
Reactant: O=C(O)c1cccc(C(=O)O)c1C(=O)O
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: O
Product: O=C(O)c1cc([N+](=O)[O-])cc(C(=O)O)c1C(=O)O

Procedure:
To a stirred mixture of 125 g. of 1,2,3-benzenetricarboxylic acid and 900 ml. of concentrated sulfuric acid at 60°-70° C. is added, gradually over a 2 hour period, 312 g. of potassium nitrate. The mixture is heated at 135°-140° C. for 16 hours, cooled and treated with ice and water. Some solid is seprated out and is dissolved in water. The entire aqueous mixture is extracted with ether, the extract is washed with water and dried over magnesium sulfate. The ether is concentrated to a small volume, and petroleum ether is added to precipitate a white solid. The solid is collected and dried to give 76.5 g. of the product of the Example.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3][C:2]=1[NH2:8].Cl[CH2:10][CH:11]=O>C(O)C.C([O-])(O)=O.[Na+]>[N:8]1[CH:10]=[CH:11][N:1]2[CH:6]=[CH:5][C:4]([NH2:7])=[N:3][C:2]=12
Reactant: Nc1ccnc(N)n1
Reactant: O=CCCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: Nc1ccn2ccnc2n1
Temperature: 70 °C
Reaction time: 8 h
Yield: 60.7 %

Procedure:
To the solution of pyrimidine-2,4-diamine (3.0 g, 0.027 mol) in ethanol (90 mL) and aqueous NaHCO3 (2M, 20 mL) was added 2-chloroacetaldehyde (4.3 g, 0.055 mol). The mixture was stirred at 70° C. overnight. TLC showed the starting material disappeared. The solvent was removed under reduced pressure and the residue was extracted with ethyl acetate (3×30 mL). The combined organic layer was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 1:5 petroleum ether/ethyl acetate to afford 199a as a white solid (2.2 g, 60%). MS: [M+H]+ 135.1.
Reaction SMILES: Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:10]=[C:11]([CH:15]=[C:16]([Cl:18])[N:17]=2)[C:12]([NH2:14])=[O:13])[CH2:5][CH2:4]1.[CH2:19]([C:21]1[C:25]([CH3:26])=[C:24]([CH3:27])[NH:23][C:22]=1[C:28](O)=[O:29])[CH3:20]>>[Cl:18][C:16]1[CH:15]=[C:11]([CH:10]=[C:9]([N:6]2[CH2:5][CH2:4][CH:3]([NH:2][C:28]([C:22]3[NH:23][C:24]([CH3:27])=[C:25]([CH3:26])[C:21]=3[CH2:19][CH3:20])=[O:29])[CH2:8][CH2:7]2)[N:17]=1)[C:12]([NH2:14])=[O:13]
Reactant: NC(=O)c1cc(Cl)nc(N2CCC(N)CC2)c1
Reactant: CCc1c(C(=O)O)[nH]c(C)c1C
Agent: Cl
Product: CCc1c(C(=O)NC2CCN(c3cc(C(N)=O)cc(Cl)n3)CC2)[nH]c(C)c1C

Procedure:
Title compound was synthesized by an analogous method to Example 18 by coupling 2-(4-aminopiperidin-1-yl)-6-chloroisonicotinamide hydrochloride (Intermediate 70) with 3-ethyl-4,5-dimethyl-1H-pyrrole-2-carboxylic acid (commercially available).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][CH:6]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:5]2.C([Li])CCC.C([O:27][B:28](OC(C)C)[O:29]C(C)C)(C)C.Cl>CCCCCC.C1COCC1>[CH2:11]([CH:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([B:28]([OH:29])[OH:27])[CH:3]=2)[CH2:7]1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCC1Cc2ccc(Br)cc2C1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCCCCCCC1Cc2ccc(B(O)O)cc2C1
Temperature: -70 °C
Reaction time: 2 h
Yield: 70 %

Procedure:
In a 200 ml-reaction vessel, 3.16 g (1.02×10-2M) of 5-bromo-2-n-octylindan and 45 ml of dry THF were placed. To the mixture, 1.5M-solution of n-butyllithium in 7.2 ml of hexane was added dropwise in 20 minutes at -70° C. under argon atmosphere, followed by stirring for 2 hours at -70° C. To the above mixture, a solution of 4.14 g (2.20×10-2M) of triisopropylborate in 9 ml of dry THF was added dropwise in 20 minutes below -70° C., followed by stirring for 1 hour at the same temperature, gradual restoration to room temperature and further stirring for 20 hours. After the reaction, 15 ml of 10%-HCl aqueous solution was added dropwise to the reaction mixture to be decomposed under cooling, followed by extraction with ether. The ether layer was washed with water and dried with anhydrous sodium sulfate, followed by distilling-off of the solvent and purification by silica gel column chromatography to obtain 1.96 g of 2-octylindan-5-boronic acid (Yield: 70%).