Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C12BC(CCC1)CCC2.O1CCN(/[C:16](/[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:17]/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)CC1>O1CCCC1>[C:18]1(/[CH:17]=[CH:16]\[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: C(=C(\c1ccccc1)N1CCOCC1)\c1ccccc1
Agent: B1C2CCCC1CCC2
Solvent: C1CCOC1
Product: C(=C\c1ccccc1)\c1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 64.9 %

Procedure:
To a mixture of 1.22 g (10.0 mmoles) of solid 9-borabicyclo[3.3.1]nonane (9-BBN) and 2.66 g (10.0 mmoles) of [E]-1-morpholino-1,2-diphenylethene is added 5.0 ml of tetrahydrofuran (THF). The mixture is stirred at 25° C. for 12 hours. The THF is removed under a pressure of about 12 Torr at 25° C. at the end of the 12 hours. The residue is dissolved in 10 ml of methanol and stirred at 25° C. for an additional 12 hours. A by-product, 9-methoxy-9-borabicyclo[3.3.1]nonane morpholine complex crystallizes out of the reaction mixture and is separated by filtration. The methanol is evaporated from the filtrate and the residue is distilled under reduced pressure. The product, 1.17 g of [Z]-1,2-diphenylethene is produced in a yield of 65 percent based on the [E]-1-morpholino-1,2-diphenylethene. The product has a boiling point of 82° C.-84° C. at 0.4 Torr. The stereochemistry of the product is confirmed by 1H and 13C NMR spectroscopy. None of the [E] isomer is detected.
Reaction SMILES: [Sn](Cl)Cl.Cl.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([N+:27]([O-])=O)=[C:10]([CH:26]=1)[CH2:11][N:12]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[C:13]1[C:21](OCC)=[O:22]>C(O)C>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]2[NH:27][C:21](=[O:22])[C:13]3=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][N:12]3[CH2:11][C:10]=2[CH:26]=1
Reactant: CCOC(=O)c1cc(C(F)(F)F)cn1Cc1cc(Cl)ccc1[N+](=O)[O-]
Agent: Cl
Agent: Cl[Sn]Cl
Solvent: CCO
Product: O=C1Nc2ccc(Cl)cc2Cn2cc(C(F)(F)F)cc21
Reaction time: 26 h
Yield: 38.8 %

Procedure:
Add tin dichloride (3 equiv; 3.02 g, 15.77 mmol) in 5M hydrochloric acid (20 mL, 100 mmol) to ethyl 1-(5-chloro-2-nitrobenzyl)-4-(trifluoromethyl)-1H-pyrrole-2-carboxylate (1 equiv; 1.98 g, 5.26 mmoles) and ethanol (100 mL) at 50° C. Heat overnight and then for a further 26 h, remove most of the ethanol in vacuo and dilute the resultant solution with water and collect the resultant precipitate by filtration, wash well with water and dry in vacuo at 40° C. Absorb the solid onto silica, chromatograph eluting with DCM/methanol (5:95) to give uncyclised amino ester (0.260 g) and 7-chloro-2-(trifluoromethyl)-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one (0.613 g). Heat the uncyclised ester in a mixture of 5M hydrochloric acid (10 mL, 50 mmol) for 80 h. Remove the ethanol in vacuo and collect the resultant precipitated solid by filtration and wash with water to give 7-chloro-2-(trifluoromethyl)-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one (0.17 g). Combine with earlier 7-chloro-2-(trifluoromethyl)-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one to give (0.794 g, 50% yield). MS (m/z): 300.99 (M+1).
Reaction SMILES: [CH2:1]([N:3]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][CH:5]=[N:4]1)[CH3:2].[B-](F)(F)(F)[F:14].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1.C(#N)C>C(O)(=O)C>[CH2:1]([N:3]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([F:14])[CH:5]=[N:4]1)[CH3:2]
Reactant: CCOC(=O)c1ccnn1CC
Reactant: F[B-](F)(F)F
Agent: F[N+]12CC[N+](CCl)(CC1)CC2
Solvent: CC(=O)O
Solvent: CC#N
Product: CCOC(=O)c1c(F)cnn1CC
Temperature: 100 °C

Procedure:
A microwave vial was charged with ethyl 1-ethyl-1H-pyrazole-5-carboxylate (0.2 g) and Selectfluor™ (0.548 g) followed by acetonitrile (3 ml) and acetic acid (0.5 ml). The mixture was heated at 100° C. under microwave irradiation for 120 min. Selectfluor™ (0.548 g) was added and the mixture was heated was heated at 100° C. under microwave irradiation for 60 min. The solvent was removed in vacuo and the residue was partitioned between DCM (15 ml) and water (15 ml) and separated by hydrophobic frit. The aqueous layer was washed with dichloromethane (2×5 ml) and the combined organic layers concentrated in vacuo. Purification by chromatography on silica gel (20 g silica cartridge) eluting with a gradient of 0-50% DCM in cyclohexane over 20 min gave the title compound (67 mg) as a colourless oil.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][NH2:9])[CH:5]=[N:4][CH:3]=[N:2]1.C(=O)(O)[O-].[Na+].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>ClCCl>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:9][CH2:8][CH2:7][CH2:6][N:1]2[CH:5]=[N:4][CH:3]=[N:2]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: NCCCn1cncn1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=S(=O)(NCCCn1cncn1)c1ccc(Cl)cc1
Reaction time: 24 h

Procedure:
To a stirred mixture of 1.89 g of 1H-1,2,4-triazole-1-propanamine in 50 ml of dichloromethane containing an excess of saturated sodium bicarbonate solution was added, all at once, 3.17 g of 4-chlorobenzenesulfonyl chloride. Vigorous stirring was continued for 24 hours. The layers were separated and the organic layer was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to give a gum.
Reaction SMILES: [OH:1][CH:2]1[CH:7]2[CH2:8][CH2:9][N:4]([CH2:5][CH2:6]2)[CH2:3]1.[I:10][C:11]1[CH:16]=[CH:15][C:14](I)=[CH:13][CH:12]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[I:10][C:11]1[CH:16]=[CH:15][C:14]([O:1][CH:2]2[CH:7]3[CH2:8][CH2:9][N:4]([CH2:5][CH2:6]3)[CH2:3]2)=[CH:13][CH:12]=1
Reactant: OC1CN2CCC1CC2
Reactant: Ic1ccc(I)cc1
Agent: c1cnc2c(c1)ccc1cccnc12
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: Ic1ccc(OC2CN3CCC2CC3)cc1
Temperature: 110 °C
Reaction time: 40 h

Procedure:
Under N2, the mixture of 3-hydroxy quinuclidine (Aldrich, 2.54 g, 20 mmol), 1,4-diiodobenzene (Aldrich, 7.9 g, 24 mmol), Cul (Strem Chemicals, 0.38 g, 2 mmol) and 1,10-phenanthroline (Aldrich, 0.72 g, 4 mmol) in toluene (anhydrous, Aldrich, 50 mL) was stirred at 110° C. for 40 h. After the reaction went to completion, the reaction mixture was diluted with chloroform (100 mL) and washed with water (2×10 mL). The organic solution was concentrated and the title compound was purified by chromatography (SiO2, CH2Cl2:MeOH:NH3.H2O, 90:10:1, Rf. 0.20) as oil (3.7 g, yield, 56%). 1H NMR (300 MHz, CD3OD) δ 1.40-1.56 (m, 1H), 1.64-1.80 (m, 2H), 1.90-2.08 (m, 1H), 2.10-2.21 (m, 1H), 2.60-3.00 (m, 5H), 3.34-3.40 (m, 1H), 4.46 (m, 1H), 6.73 (d, J=8.8 Hz, 2H), 7.56 (d, J=8.8, Hz, 2H), ppm. MS (DCI/NH3) m/z 330 (M+H)+.
Reaction SMILES: [C:1]1([C:7]2[C:8](=[O:33])[NH:9][C:10](=[O:32])[N:11]([CH2:13][CH2:14][CH2:15][N:16]3[CH2:21][CH:20]4[C@:18]([C:22]5[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=5)([CH2:19]4)[CH2:17]3)[N:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:34]>C(OCC)C>[ClH:34].[C:1]1([C:7]2[C:8](=[O:33])[NH:9][C:10](=[O:32])[N:11]([CH2:13][CH2:14][CH2:15][N:16]3[CH2:21][C@H:20]4[C@:18]([C:22]5[CH:23]=[CH:24][C:25]([C:28]([F:30])([F:31])[F:29])=[CH:26][CH:27]=5)([CH2:19]4)[CH2:17]3)[N:12]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=c1[nH]c(=O)n(CCCN2CC3C[C@]3(c3ccc(C(F)(F)F)cc3)C2)nc1-c1ccccc1
Agent: Cl
Solvent: CCOCC
Product: O=c1[nH]c(=O)n(CCCN2C[C@@H]3C[C@]3(c3ccc(C(F)(F)F)cc3)C2)nc1-c1ccccc1
Yield: 27 %

Procedure:
6-phenyl-2-(3-{(1S)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (9 mg 0.019 mmol) was diluted in diethyl ether (1 ml) and hydrochloric acid 1M in Et2O (0.022 ml, 0.022 mmol) under nitrogen atmosphere. Solvent was removed and the residue triturated in Et2O (2×1 mL), obtaining 3.2 mg of title compound as a white solid (27% yield).
Reaction SMILES: [BH4-].[Na+].[CH3:3][NH:4][CH:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[C:7](=[O:16])[CH2:6]1>O.C(O)C>[CH3:3][NH:4][CH:5]1[CH2:11][CH2:10][C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[CH:7]([OH:16])[CH2:6]1
Reactant: CNC1CCc2ccccc2C(=O)C1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CNC1CCc2ccccc2C(O)C1
Reaction time: 0.5 h
Yield: 104.2 %

Procedure:
A solution of 47.5g of sodium borohydride in 475 ml of water was slowly added to a solution of 47.5 g of the product of Step A in 2.4 liters of ethanol and the mixture was stirred for 2 1/2 hours and then was concentrated to 500 ml. The mixture was poured into 2 liters of aqueous sodium chloride solution and the mixture was extracted with ethyl acetate. The organic phase was washed with aqueous sodium chloride solution, dried and evaporated to dryness to obtain 50 g of raw 7-methylamino-5-hydroxy-6,7,8,9-tetrahydro [5H] benzocycloheptene which was used as is for the next step.
Reaction SMILES: [CH3:1][C@H:2]1[O:18][C:16](=[O:17])[CH2:15][C@@H:14]([O:19][C:20]([CH3:22])=[O:21])[C@H:13]([O:23][CH3:24])[C@@H:12]([O:25][C@@H:26]2[O:31][C@H:30]([CH3:32])[C@@H:29]([O:33][C@@H:34]3[O:39][C@@H:38]([CH3:40])[C@H:37]([O:41][C:42]([CH2:44][CH:45]([CH3:47])[CH3:46])=[O:43])[C@@:36]([OH:49])([CH3:48])[CH2:35]3)[C@H:28]([N:50]([CH3:52])[CH3:51])[C@H:27]2[OH:53])[C@@H:11]([CH2:54][CH:55]=[O:56])[CH2:10][C@@H:9]([CH3:57])[C@@H:8]([OH:58])[CH:7]=[CH:6][CH:5]=[CH:4][CH2:3]1.C(Cl)Cl>CS(C)=O.C(N(CC)CC)C>[CH3:1][C@H:2]1[O:18][C:16](=[O:17])[CH2:15][C@@H:14]([O:19][C:20]([CH3:22])=[O:21])[C@H:13]([O:23][CH3:24])[C@@H:12]([O:25][CH:26]2[O:31][CH:30]([CH3:32])[CH:29]([O:33][CH:34]3[O:39][CH:38]([CH3:40])[CH:37]([O:41][C:42]([CH2:44][CH:45]([CH3:46])[CH3:47])=[O:43])[C:36]([OH:49])([CH3:48])[CH2:35]3)[CH:28]([N:50]([CH3:52])[CH3:51])[CH:27]2[OH:53])[C@@H:11]([CH2:54][CH:55]=[O:56])[CH2:10][C@@H:9]([CH3:57])[C:8](=[O:58])[CH:7]=[CH:6][CH:5]=[CH:4][CH2:3]1
Reactant: CO[C@@H]1[C@@H](O[C@@H]2O[C@H](C)[C@@H](O[C@H]3C[C@@](C)(O)[C@@H](OC(=O)CC(C)C)[C@H](C)O3)[C@H](N(C)C)[C@H]2O)[C@@H](CC=O)C[C@@H](C)[C@@H](O)C=CC=CC[C@@H](C)OC(=O)C[C@H]1OC(C)=O
Agent: CO[C@@H]1[C@@H](OC2OC(C)C(OC3CC(C)(O)C(OC(=O)CC(C)C)C(C)O3)C(N(C)C)C2O)[C@@H](CC=O)C[C@@H](C)C(=O)/C=C/C=C/C[C@@H](C)OC(=O)C[C@H]1OC(C)=O
Agent: CO[C@@H]1[C@@H](O[C@@H]2O[C@H](C)[C@@H](O[C@H]3C[C@@](C)(O)[C@@H](OC(=O)CC(C)C)[C@H](C)O3)[C@H](N(C)C)[C@H]2O)[C@@H](CC=O)C[C@@H](C)[C@@H](O)/C=C/C=C/C[C@@H](C)OC(=O)C[C@H]1OC(C)=O
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CO[C@@H]1[C@@H](OC2OC(C)C(OC3CC(C)(O)C(OC(=O)CC(C)C)C(C)O3)C(N(C)C)C2O)[C@@H](CC=O)C[C@@H](C)C(=O)C=CC=CC[C@@H](C)OC(=O)C[C@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
10.0 g (12.1 mmol) of leucomycin A3, also known as josamycin, are dissolved in 30 ml of DMSO and 15 ml of triethylamine. To the solution thereby obtained, 5.6 g of sulfur trioxide/pyridine complex (36.3 mmol), dissolved in 40 ml of DMSO, are added at room temperature and under a nitrogen atmosphere. The reaction medium is stirred at room temperature for 3 hours. Approximately 200 g of ice are added and the mixture is filtered: the product thereby obtained is taken up with methylene chloride and the organic phase is washed three times with water; the organic phase is dried over sodium sulfate, filtered and evaporated to dryness. The residue thereby obtained is purified by flash chromatography on a silica column; eluant: CH2Cl2 /MeOH/NH4OH (300:5:0.25). 3.6 g of carbomycin B are obtained.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([CH:13]3[CH2:15][CH2:14]3)[O:11][CH:12]=2)=[CH:4][CH:3]=1.[Cu](C#N)[C:17]#[N:18].[C-]#N.[Na+]>CN1C(=O)CCC1>[CH:13]1([C:10]2[O:11][CH:12]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:17]#[N:18])=[CH:3][CH:4]=3)[N:9]=2)[CH2:15][CH2:14]1
Reactant: Brc1ccc(-c2coc(C3CC3)n2)cc1
Reactant: N#C[Cu]C#N
Agent: [C-]#N
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: N#Cc1ccc(-c2coc(C3CC3)n2)cc1
Yield: 70.6 %

Procedure:
To a solution of 4-(4-bromophenyl)-2-cyclopropyl-1,3-oxazole (1.78 g, 6.74 mmol) in NMP (25 mL) was added copper cyanide (4.22 g, 47.12 mmol). The mixture was heated to 185C for 4 h. Upon cooling, the mixture was poured into a 0C solution of 5% aqueous sodium cyanide (60 ml). The aqueous phase was extracted with Et2O. The combined organic phases were washed with, 5% aqueous sodium cyanide, water, and brine, dried with MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (CH2Cl2/Hexanes, 2:3 to 10:0) to yield 4-(2-cyclopropy-1,3-oxazol-4-yl)benzonitrile as a yellow solid (1.00 g, 71%).
Reaction SMILES: [NH2:1][C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)=[S:3].Br[CH2:11][C:12](=O)[C:13]([O:15]CC)=[O:14].CCO.O[Li].O>CO>[N:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[C:2]1[S:3][CH:11]=[C:12]([C:13]([OH:15])=[O:14])[N:1]=1
Reactant: NC(=S)c1ccccn1
Reactant: CCOC(=O)C(=O)CBr
Agent: [Li]O
Solvent: CCO
Solvent: O
Solvent: CO
Product: O=C(O)c1csc(-c2ccccn2)n1
Temperature: 25 °C

Procedure:
Amino-2-pyridylmethane-1-thione (1.88 g, 0.0136 mol), ethyl bromopyruvate (1.80 mL, 0.0143 mol) and EtOH (30 mL) were combined and heated to reflux. GC/MS of reaction mixture after 3 h showed total consumption of the starting materials. After cooling to RT, the solvent was removed under vacuum resulting in a dark brown oil (GC/MS m/z: 235 (M+H); GC Retention time: 10.69 min). The material was taken up in MeOH (20 mL), 1.0M LiOH—H2O (20 mL) was added and the mixture was heated to 100° C. for 14 h. After cooling to RT, the excess MeOH was evaporated and the resulting brown solid filtered. The material was washed with a minimum of H2O and dried in vacuo to give the thiazole as a brown solid.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]2[C:11](=[O:16])[NH:12][NH:13][C:14]=2[CH3:15])=[CH:5][CH:4]=1)[CH3:2].[CH2:17]([C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]2[C:27]([O:32][C@@H:33]3[O:50][C@H:49]([CH2:51][O:52][C:53](=[O:55])[CH3:54])[C@@H:44]([O:45][C:46](=[O:48])[CH3:47])[C@H:39]([O:40][C:41](=[O:43])[CH3:42])[C@H:34]3[O:35][C:36](=[O:38])[CH3:37])=[N:28][NH:29][C:30]=2[CH3:31])=[CH:21][CH:20]=1)[CH3:18]>>[CH2:17]([C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]2[C:27]([O:32][C@@H:33]3[O:50][C@H:49]([CH2:51][O:52][C:53](=[O:55])[CH3:54])[C@@H:44]([O:45][C:46](=[O:48])[CH3:47])[C@H:39]([O:40][C:41](=[O:43])[CH3:42])[C@H:34]3[O:35][C:36](=[O:38])[CH3:37])=[N:28][NH:29][C:30]=2[CH3:31])=[CH:21][CH:20]=1)[CH3:18].[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:9][C:10]2[C:11]([O:16][CH:33]3[O:50][C@H:49]([CH2:51][OH:52])[C@@H:44]([OH:45])[C@H:39]([OH:40])[C@H:34]3[OH:35])=[N:12][NH:13][C:14]=2[CH3:15])=[CH:7][CH:8]=1)[CH3:2]
Reactant: CCc1ccc(Cc2c(C)[nH][nH]c2=O)cc1
Agent: CCc1ccc(Cc2c(O[C@@H]3O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)n[nH]c2C)cc1
Product: CCc1ccc(Cc2c(OC3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)n[nH]c2C)cc1

Procedure:
4-[(4-Ethylphenyl)methyl]-5-methyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole was prepared in a similar manner to that described in Reference Example 17 using 4-[(4-ethylphenyl)methyl]-1,2-dihydro-5-methyl-3H-pyrazol-3-one instead of 1,2-dihydro-4-[(4-isopropoxyphenyl)methyl]-5-methyl-3H-pyrazol-3-one. Then, the title compound was prepared in a similar manner to that described in Reference Example 37 using 4-[(4-ethylphenyl)methyl]-5-methyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole instead of 4-[(4-isopropoxyphenyl)methyl]-5-methyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[CH:11]=[C:10]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[N:9]=2)[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[C:33](=[O:35])=[O:34]>C1COCC1>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([C:12]2[CH:11]=[C:10]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[N:9]=[C:8]([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([C:33]([OH:35])=[O:34])[N:7]=3)[CH:13]=2)=[CH:15][CH:16]=1
Reactant: O=C=O
Reactant: COc1ccc(-c2cc(-c3ccccn3)nc(-c3cccc(Br)n3)c2)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1ccc(-c2cc(-c3ccccn3)nc(-c3cccc(C(=O)O)n3)c2)cc1
Temperature: -78 °C
Reaction time: 0.25 h

Procedure:
A flame dried 3 necked 1 L flask equipped with a mechanical stirrer, pressure equalizing addition funnel, and, attached via silicone rubber tubing, a Gooch tube containing solid 6-bromo-4′-(4-methoxyphenyl)-2,2′:6′2″-terpyridine (42.2 mmole) under nitrogen is charged with 400 mL THF and cooled in a Dry Ice/ether bath to −78° C. A solution of n-butyllithium (20 mL of 2.5 M) is transferred via nitrogen pump to the pressure equalizing addition funnel, and is then added to the THF solution. After stirring 15 minutes at −78° C., the solid 6-bromo-4′-(4-methoxyphenyl)-2,2′:6′2″-terpyridine is added portionwise over an 11 minute period from the Gooch tube. The temperature is not allowed to exceed −75° C. during the addition. After the addition, the bath is lowered, and the reaction mixture is allowed to warm slightly to −70° C. over a 10 minute period. The solution is re-cooled to −78° C., and the reaction mixture is transferred via cannula under nitrogen to a jacketed addition funnel cooled to −78° C. This anionic solution is maintained at −78° C. under nitrogen while it is added with stirring to 400 mL of THF saturated with anhydrous carbon dioxide in a 3 liter 3 necked flask attached to a silicone oil bubbler. Additional anhydrous carbon dioxide is slowly bubbled into the reaction mixture during the addition while the temperature is carefully controlled to remain below −70° C. After stirring for 60 minutes, the cooling bath is removed and the reaction mixture is carefully quenched with 100 ml of a 1 N aqueous HCl solution over a ten minute period. The reaction mixture is allowed to stir and warm to room temperature. The solvent is evaporated under vacuum below 20° C., the crude product is triturated with isopropanol, isolated by filtration, washed with ether and dried under vacuum.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1Br)=[O:3].[F:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1B(O)O.ClCCl.[OH-].[Na+]>O1CCCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:5]1[CH:6]=[CH:7][C:8]([F:10])=[CH:9][C:4]=1[C:2](=[O:3])[CH3:1]
Reactant: CC(=O)c1cc(F)ccc1Br
Reactant: OB(O)c1ccccc1F
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [Na+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(=O)c1cc(F)ccc1-c1ccccc1F
Temperature: 60 °C

Procedure:
A stirred solution of 2-bromo-5-fluoroacetophenone (11.72 g, 54 mmol) and 2-fluorophenylboronic acid (7.55 g, 54 mmol) in tetrahydrofuran (600 mL) was treated under nitrogen with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (2.20 g, 2.69 mmol, 5 mole %) and a 5 N sodium hydroxide solution (21.6 mL, 108 mmol). The reaction was heated at 60° C. for twelve hours, cooled to room temperature, and the solvent removed in vacuo. The residue was dissolved in diethyl ether, filtered through a short column of silica gel, and the solvent evaporated in vacuo to a crude brown oil (11.72 g). The crude oil was purified by repetitive, preparative, liquid chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g), eluting with a gradient of between 3% and 10% methyl tert-butylether in hexane at a flow rate of 50 mL/min to afford, after evaporation of the solvent, the title compound as a purified, colorless oil (10.2 g, 43.9 mmol, 81%).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[C:6]([NH2:12])[C:7]([NH2:11])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.O.[C:14](O)(=[O:18])[C:15](O)=[O:16]>Cl>[NH:12]1[C:6]2[C:5]3[CH:4]=[CH:3][CH:2]=[N:1][C:10]=3[CH:9]=[CH:8][C:7]=2[NH:11][C:15](=[O:16])[C:14]1=[O:18]
Reactant: O=C(O)C(=O)O
Reactant: Nc1ccc2ncccc2c1N
Agent: Cl
Solvent: O
Product: O=c1[nH]c2ccc3ncccc3c2[nH]c1=O
Yield: 81.3 %

Procedure:
A mixture of 5,6-quinolinediamine (11.3 g, 0.071 mol) and oxalic acid hydrate (17.9 g, 0.142 mol) in 200 mL 2N HCl was heated at reflux for 2 hours. The solid (12.3 g, 83% yield) was collected by filtration and washed consecutively with water and ether.
Reaction SMILES: [Na].Cl[C:3]1[N:8]=[C:7](Cl)[C:6]([F:10])=[CH:5][N:4]=1.[CH2:11]([OH:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1(C)C=CC=CC=1>[CH2:11]([O:18][C:3]1[N:8]=[C:7]([O:18][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:6]([F:10])=[CH:5][N:4]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: OCc1ccccc1
Reactant: Fc1cnc(Cl)nc1Cl
Agent: [Na]
Solvent: Cc1ccccc1
Product: Fc1cnc(OCc2ccccc2)nc1OCc1ccccc1
Yield: 87.1 %

Procedure:
A 5.8 g quantity of metal sodium is dissolved in a mixture of 100 ml of benzyl alcohol and 200 ml of toluene, 16.7 g of 2,4-dichloro-5-fluoropyrimidine is added to the solution, and the mixture is refluxed for 4 hours. The resulting reaction mixture is washed with water, dried and distilled at reduced pressure to give 27.0 g of colorless oily 2,4-di(benzyloxy)-5-fluoropyrimidine in a yield of 87.1 %, b.p. 205°-206° C/3-4 mm Hg and m.p. 48.5°-49.5° C.
Reaction SMILES: [C:1]([C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[N:16]1[C:20]([CH2:21][Cl:22])=[N:19][C:18]([C:23]([O:25]CC)=[O:24])=[N:17]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.[OH-].[Na+]>C(O)(=O)C>[C:1]([C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[N:16]1[C:20]([CH2:21][Cl:22])=[N:19][C:18]([C:23]([OH:25])=[O:24])=[N:17]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1nc(CCl)n(-c2ccc(Cl)cc2C(=O)c2ccccc2)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CC(=O)O
Product: O=C(O)c1nc(CCl)n(-c2ccc(Cl)cc2C(=O)c2ccccc2)n1
Reaction time: 0.25 h

Procedure:
To a solution of 6.0 parts of ethyl 1-(2-benzoyl-4-chlorophenyl)-5-chloromethyl-1H-1,2,4-triazole-3-carboxylate in 70 volume parts of methanol is added 16.5 volume parts of 1N sodium hydroxide dropwise. The hydrolysis is completed after about 15 minutes. Then, acetic acid is added to the reaction mixture to make acidic and the solvent is distilled off under reduced pressure. To the residue is added water and the precipitate is collected by filtration. The procedure gives 1-(2-benzoyl-4-chlorophenyl)-5-chloromethyl-1H-1,2,4-triazole-3-carboxylic acid as crystals. Recrystallization from ether gives colorless prisms melting at 176°-177°C.
Reaction SMILES: [O-:1][C:2]#[N:3].[Na+].[NH2:5][C:6]1[CH:10]=[CH:9][S:8][C:7]=1[C:11]([O:13]C)=O>O.C(O)(=O)C>[NH:5]1[C:6]2[CH:10]=[CH:9][S:8][C:7]=2[C:11](=[O:13])[NH:3][C:2]1=[O:1]
Reactant: N#C[O-]
Reactant: COC(=O)c1sccc1N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: O=c1[nH]c(=O)c2sccc2[nH]1
Temperature: 25 °C
Reaction time: 5 h
Yield: 80.5 %

Procedure:
To a solution in which sodium cyanate (5.0 g, 77.0 mmol) was dissolved in water (15.0 mL), methyl 3-aminothiophen-2-carboxylate (6.05 g, 38.4 mmol) dissolved in a mixture solution (90 mL) of 50% glacial acetic acid and water was slowly added dropwise. After stirring for 5 hours at room temperature, thus prepared white precipitate was filtered. The white solid was dissolved in 2.0 N sodium hydroxide solution (90.0 mL). The mixture solution was cooled to 0° C. and acidified using acetic acid. Filtration of thus prepared white solid followed by drying yielded the target compound thieno[3,2-d]pyrimidin-2,4(1H,3H)-dione (5.2 g, 81% yield).
Reaction SMILES: [C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:8]([N:10]=[C:11]=[O:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:19]([OH:24])[CH2:20][CH2:21][C:22]#[CH:23]>>[CH2:19]([O:24][C:11](=[O:12])[NH:10][C:8](=[O:9])[CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:20][CH2:21][C:22]#[CH:23]
Reactant: C#CCCCO
Reactant: O=C=NC(=O)C(c1ccccc1)c1ccccc1
Product: C#CCCCOC(=O)NC(=O)C(c1ccccc1)c1ccccc1

Procedure:
The title compound, white solid, m.p. 109° C. and MS: m/e=321.4 (M+H+) was prepared in accordance with the general method of example 1 from diphenylacetyl isocyanate and pent-4yn-1-ol.