Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:41])[N:7]([CH2:11][C@H:12]1[C@@H:16]([CH2:17][N:18]([CH:31]([CH3:33])[CH3:32])S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[CH2:15][N:14]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:13]1)[CH:8]([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].SCCO.C1CCN2C(=NCCC2)CC1>CC#N>[C:1]([O:5][C:6](=[O:41])[N:7]([CH2:11][C@H:12]1[C@@H:16]([CH2:17][NH:18][CH:31]([CH3:33])[CH3:32])[CH2:15][N:14]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:13]1)[CH:8]([CH3:10])[CH3:9])([CH3:3])([CH3:2])[CH3:4]
Reactant: CC(C)N(C[C@@H]1CN(Cc2ccccc2)C[C@@H]1CN(C(C)C)S(=O)(=O)c1ccccc1[N+](=O)[O-])C(=O)OC(C)(C)C
Agent: OCCS
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: CC(C)NC[C@H]1CN(Cc2ccccc2)C[C@H]1CN(C(=O)OC(C)(C)C)C(C)C

Procedure:
A solution of ((3S*,4R*)-1-benzyl-4-{[isopropyl-(2-nitro-benzenesulfonyl)-amino]-methyl}-pyrrolidin-3-ylmethyl)-isopropyl-carbamic acid tert-butyl ester (8.9 g, 23.02 mmol), 2-mercaptoethanol (0.81 mL, 11.60 mmol), and DBU (0.79 mL, 5.27 mmol) in CH3CN (10 mL) is stirred for 2 h at room temperature. The mixture is concentrated and then diluted with Et2O and H2O. The organic layer is separated, and the aqueous phase is extracted 3 times with Et2O. The combined organic extracts are dried (MgSO4), and the solvent is concentrated to give the title compound which is used without further purification in the next step. TLC, Rf (AcOEt)=0.61. MS (LC-MS): 404.3 [M+H]+; tR (HPLC, C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/2.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 4.45 min.
Reaction SMILES: [CH2:1]([O:13][C:14]1[N:15]=[C:16]([Si:19]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[S:17][CH:18]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[Li][CH2:30][CH2:31][CH2:32][CH3:33]>C1COCC1>[CH2:1]([O:13][C:14]1[N:15]=[C:16]([Si:19]([CH:26]([CH3:27])[CH3:28])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:21])[CH3:22])[S:17][C:18]=1[C:18]1[S:17][C:16]([Si:19]([CH:23]([CH3:24])[CH3:25])([CH:26]([CH3:27])[CH3:28])[CH:20]([CH3:22])[CH3:21])=[N:15][C:14]=1[O:13][CH2:30][CH2:31][CH2:32][CH2:33][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: [Li]CCCC
Reactant: CCCCCCCCCCCCOc1csc([Si](C(C)C)(C(C)C)C(C)C)n1
Solvent: C1CCOC1
Product: CCCCCCCCCCCCOc1nc([Si](C(C)C)(C(C)C)C(C)C)sc1-c1sc([Si](C(C)C)(C(C)C)C(C)C)nc1OCCCCCCCCCCCC
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 96.1 %

Procedure:
A solution of 6.24 g (14.7 mmol) of compound 11 in 150 mL of THF was cooled to −78° C. and treated dropwise with 6.45 mL (16.1 mmol) of n-BuLi (2.5 M in hexanes). The mixture was stirred for 45 minutes, then the dry ice bath was removed and the mixture was stirred at ambient temperature for 1 hour. The mixture was cooled to 0° C. and treated with 5.69 g (16.1 mmol) of Fe(acac)3 (Strem Chemicals, Inc.). The mixture was heated in an 80° C. oil bath for 2 h, cooled to room temperature, and filtered. The filter cake was washed with 3×25 mL of THF. The filtrate was concentrated in vacuo and purified by flash chromatography (silica gel, 5.5×35 cm, chloroform) to give 6.0 g (96% yield) of compound 12 as a yellow oil. 1H NMR (500 MHz) δ 4.51 (t, 4H, J=6.3 Hz), 1.86-0.88 (m, 88H).
Reaction SMILES: [CH3:1][OH:2].N1C=CC=CC=1.[Cl:9][C:10]1[N:18]=[C:17]([Cl:19])[CH:16]=[C:15]([C:20]([F:23])([F:22])[F:21])[C:11]=1[C:12](Cl)=[O:13]>ClCCl>[Cl:9][C:10]1[N:18]=[C:17]([Cl:19])[CH:16]=[C:15]([C:20]([F:23])([F:22])[F:21])[C:11]=1[C:12]([O:2][CH3:1])=[O:13]
Reactant: O=C(Cl)c1c(C(F)(F)F)cc(Cl)nc1Cl
Reactant: CO
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)c1c(C(F)(F)F)cc(Cl)nc1Cl
Reaction time: 1 h

Procedure:
100 ml of methanol and 4.37 ml (53.9 mmol) of pyridine were cooled in an ice-bath. A solution of 10.0 g (35.9 mmol) of 2,6-dichloro-4-(trifluoromethyl)nicotinoyl chloride [Y. Tsuzuki et al., J. Med. Chem. 47, 2097-2109 (2004)] in 40 ml of dichloromethane was then added dropwise. The mixture was stirred with ice-cooling for one hour and then at room temperature for one hour. The reaction mixture was concentrated on a rotary evaporator. The residue was taken up in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution and then with saturated aqueous sodium chloride solution. The organic phase was dried with magnesium sulfate and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (silica gel: isohexane/ethyl acetate=95/5). This gave 8.98 g (91% of theory) of the target compound.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:13][CH:12]([OH:14])[CH2:11]2)=[N:8][CH:9]=1)([O-])=O.[C:15]1([C:21]2[O:22][C:23]([C:29]([F:32])([F:31])[F:30])=[C:24]([C:26](O)=[O:27])[N:25]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CCN(CC)CC.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CCO.C(O)(=O)C.[Pd]>[OH:14][CH:12]1[CH2:13][N:10]([C:7]2[N:8]=[CH:9][C:4]([NH:1][C:26]([C:24]3[N:25]=[C:21]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[O:22][C:23]=3[C:29]([F:31])([F:32])[F:30])=[O:27])=[CH:5][CH:6]=2)[CH2:11]1
Reactant: O=C(O)c1nc(-c2ccccc2)oc1C(F)(F)F
Reactant: O=[N+]([O-])c1ccc(N2CC(O)C2)nc1
Agent: [Pd]
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCO
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Product: O=C(Nc1ccc(N2CC(O)C2)nc1)c1nc(-c2ccccc2)oc1C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 10.1 %

Procedure:
1-(5-Nitro-pyridin-2-yl)-azetidin-3-ol (400 mg, 2 mmol) was hydrogenated at 35 psi for 2¾ hrs with 10% Pd/C (40 mg) in EtOH (30 mL) and acetic acid (2 drops). The mixture was filtered through a celite plug, evaporated and then co-evaporated with toluene. The residue was dissolved in DMF (15 mL). One half of this solution (7.5 mL, ˜1 mmol) was removed. To this was added 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (257 mg, 1 mmol), Et3N (422 uL, 3 mmol) and BOP (464 mg. 1.05 mmol). The reaction was stirred for 1 hr at room temperature. Following work-up as above, the crude material was purified by flash chromatography to yield 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [6-(3-hydroxyazetidin-1-yl)-pyridin-3-yl]-amide as an off-white solid (41 mg). ES-MS calcd for C19H15F3N4O3 (m/e) 404.35, obsd 405.1 (M+H).
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:21]=[CH:20][C:15]([C:16](OC)=[O:17])=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].C([O-])([O-])=O.[K+].[K+].OC1C=CC(C=O)=CC=1.[Br:37]CCCCCCCCCCBr>>[Br:37][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][O:11][C:12]1[CH:21]=[CH:20][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1
Reactant: CCCCCCCCCCOc1ccc(C(=O)OC)cc1
Reactant: BrCCCCCCCCCCBr
Agent: O=C([O-])[O-]
Agent: O=Cc1ccc(O)cc1
Agent: [K+]
Product: O=Cc1ccc(OCCCCCCCCCCBr)cc1

Procedure:
Synthesized as described above for compound 1. Quantities: K2CO3 (4.75 g, 34 mmol), p-hydroxybenzaldehyde (3.57 g, 29 mmol), 1,10-dibromodecane (8.6 mL, 38 mmol). Yield 10.0 g (quant.). 1H NMR: δH (CDCl3; 300 MHz): 1.22-1.52 (12 H, m, CH2), 1.80 (4 H, m, O—CH2—CH2/Br—CH2—CH2), 3.36 (2 H, t, 3J=6.9 Hz, Br—CH2), 4.00 (2 H, t, 3J=6.5 Hz, O—CH2), 6.95 (2 H, d, 3J=8.7 Hz, Ar—H), 7.79 (2 H, d, 3J =8.8 Hz, Ar—H), 9.84 (1 H, s, COH). 13C NMR: δC (CDCl3; 75 MHz): 25.9, 28.1, 28.7, 29.0, 29.3, 29.4, 29.5, 32.8, 34.0, 68.4, 114.7, 129.7, 131.9, 164.2, 190.7.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[N:11]=[CH:10][N:9]=[C:8]([S:12][CH2:13][CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:6]=2[N:7]=1.[NH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>>[O:25]1[CH2:26][CH2:27][N:22]([C:4]2[C:5]3[N:11]=[CH:10][N:9]=[C:8]([S:12][CH2:13][CH2:14][CH2:15][C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[C:6]=3[N:7]=[C:2]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)[N:3]=2)[CH2:23][CH2:24]1
Reactant: C1CNCCN1
Reactant: Clc1nc(N2CCOCC2)c2ncnc(SCCCc3ccccc3)c2n1
Product: c1ccc(CCCSc2ncnc3c(N4CCOCC4)nc(N4CCNCC4)nc23)cc1

Procedure:
This compound was prepared analogous to Example 1 from 2-chloro-4-morpholino-8-(3-phenylpropyl-thio)-pyrimido-[5,4-d]-pyrimidine (m.p.: 127°-129° C.) and piperazine.
Reaction SMILES: [NH2:1][C:2]1[C:3](C#N)=[N:4][C:5]([Cl:9])=[CH:6][C:7]=1[Cl:8].O.[C:13](=[O:16])(O)[O-:14].[Na+]>S(=O)(=O)(O)O>[NH2:1][C:2]1[C:3]([C:13]([OH:14])=[O:16])=[N:4][C:5]([Cl:9])=[CH:6][C:7]=1[Cl:8]
Reactant: N#Cc1nc(Cl)cc(Cl)c1N
Reactant: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: Nc1c(Cl)cc(Cl)nc1C(=O)O
Temperature: 100 °C
Reaction time: 1 h

Procedure:
3-Amino-4,6-dichloro-pyridine-2-carbonitrile (121 mg) was dissolved in concentrated sulfuric acid (1 mL) and stirred for 1 h at 100° C. The reaction mixture was cooled to room temperature and water (1 mL) was slowly added. The reaction mixture was warmed again to 100° C. and stirred at this temperature for 2 h. Water was added after cooling to room temperature, the pH was adjusted to ˜10 by addition of solid sodium bicarbonate and the aqueous solution was washed 2× with MTB-ether. The aqueous layer was then adjusted to pH ˜2 by addition of 2 M hydrochloric acid and extracted 3× with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuum to afford 99 mg of the title compound of the formula
Reaction SMILES: Cl.CN(C)CCCN=C=NCC.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]([OH:22])=O)=[N:18][CH:19]=1.[F:23][C:24]1([F:45])[CH2:44][CH2:43][C:27]2([C:35]3([N:39]=[C:38]([NH2:40])[C:37]([CH3:41])=[N:36]3)[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([NH2:42])[CH:33]=3)[CH2:28]2)[CH2:26][CH2:25]1.Cl>C(Cl)Cl.CN(C=O)C>[NH2:40][C:38]1[C:37]([CH3:41])=[N:36][C:35]2([C:34]3[C:29](=[CH:30][CH:31]=[C:32]([NH:42][C:20]([C:17]4[CH:16]=[CH:15][C:14]([Cl:13])=[CH:19][N:18]=4)=[O:22])[CH:33]=3)[CH2:28][C:27]32[CH2:26][CH2:25][C:24]([F:45])([F:23])[CH2:44][CH2:43]3)[N:39]=1
Reactant: CC1=NC2(N=C1N)c1cc(N)ccc1CC21CCC(F)(F)CC1
Reactant: O=C(O)c1ccc(Cl)cn1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC1=NC2(N=C1N)c1cc(NC(=O)c3ccc(Cl)cn3)ccc1CC21CCC(F)(F)CC1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 17.2 %

Procedure:
N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (36 mg, 0.19 mmol) was added to a suspension of 5-chloropicolinic acid (27 mg, 0.17 mmol) in DCM (0.5 mL). The obtained orange solution was stirred for 5 min and then added dropwise over 2 min to an ice-cooled solution of 4,4-difluoro-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazole]-4″,6′-diamine (Example 28d Step 1, 46 mg, 0.14 mmol) and 2M aq. HCl (0.072 mL, 0.14 mmol) in DMF (0.5 mL). The mixture was stirred at 0° C. for 10 min and was then allowed to reach r.t. overnight. The solvent was evaporated. The crude was purified using preparative chromatography to give the title compound (11 mg, 17% yield): 1H NMR (500 MHz, DMSO-d6) δ ppm 1.23 (d, 1 H), 1.51 (d, 2 H), 1.66-1.98 (m, 5 H), 2.18 (s, 3 H), 2.99 (d, 1 H), 3.08 (d, 1 H), 6.63 (br. s., 1 H), 7.23-7.29 (m, 2 H), 7.62 (d, 1 H), 8.10 (d, 1 H), 8.18 (dd, 1 H), 8.74 (s, 1 H), 10.50 (s, 1 H); MS (APCI+) m/z 458.1 [M+H]+.
Reaction SMILES: [OH:1][CH2:2][CH:3]([C:22]1[CH:43]=[CH:42][C:25]([C:26]([NH:28][C@H:29]([C:37]([O:39]CC)=[O:38])[CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])=[O:27])=[CH:24][CH:23]=1)[CH2:4][N:5]1[C:10]([OH:11])=[C:9]2[CH:12]=[C:13]([NH:15]C(=O)C(C)(C)C)[N:14]=[C:8]2[N:7]=[CH:6]1.Cl>[OH-].[Na+]>[OH:1][CH2:2][CH:3]([C:22]1[CH:43]=[CH:42][C:25]([C:26]([NH:28][C@H:29]([C:37]([OH:39])=[O:38])[CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[O:27])=[CH:24][CH:23]=1)[CH2:4][N:5]1[C:10]([OH:11])=[C:9]2[CH:12]=[C:13]([NH2:15])[N:14]=[C:8]2[N:7]=[CH:6]1
Reactant: CCOC(=O)CC[C@H](NC(=O)c1ccc(C(CO)Cn2cnc3nc(NC(=O)C(C)(C)C)cc-3c2O)cc1)C(=O)OCC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Nc1cc2c(O)n(CC(CO)c3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)cnc-2n1

Procedure:
A solution of 0.3 g of diethyl N-[4-{1-hydroxy-3-(4-hydroxy-6-pivaloylaminopyrrolo[2,3-d]pyrimidin-3-yl)prop-2-yl}benzoyl]glutamate in 9 ml of 1N aqueous sodium hydroxide is stirred under nitrogen at ambient temperature for 72 hours. The reaction mixture is rendered slightly acidic (pH=-4) with 1N hydrochloric acid and filtered. The solid thus collected is washed with water (5 ml) and cold ethanol (5 ml) and dried to give N-[4-(1-hydroxy-3-(4-hydroxy-6-aminopyrrolo[2,3-d]-pyrimidin-3-yl)prop-2-yl)benzoyl]glutamic acid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1[O:23][CH3:24])=[O:11].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[C:54]([O:58][CH3:59])(=[O:57])[CH:55]=[CH2:56]>C(#N)C(C)C.CC#N.CC#N.Cl[Pd]Cl.O>[CH3:59][O:58][C:54](=[O:57])[CH2:55][CH:56]1[C:2]2[C:3](=[C:4]([F:8])[CH:5]=[CH:6][CH:7]=2)[NH:9][C:10](=[O:11])[N:12]1[C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1[O:23][CH3:24]
Reactant: COc1ccc(C(F)(F)F)cc1NC(=O)Nc1c(F)cccc1Br
Reactant: C=CC(=O)OC
Agent: Cl[Pd]Cl
Agent: CC(C)C#N
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: O
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COC(=O)CC1c2cccc(F)c2NC(=O)N1c1cc(C(F)(F)F)ccc1OC
Temperature: 95 °C
Reaction time: 22 h
Yield: 75 %

Procedure:
N-(2-Bromo-6-fluorophenyl)-N′-[2-methoxy-5-(trifluoromethyl)phenyl]urea (2.5 kg) is suspended in isobutyronitrile under a nitrogen atmosphere (9 l), then triethylamine (1.31 kg), bis(acetonitrile)dichloropalladium (64.9 g), tris(o-tolyl)phosphine (149 g) and methyl acrylate (1.59 kg) are added in this sequence. The resulting suspension is stirred at 90-100° C. for 22 h, then cooled to room temperature. Water (9 l) is added and the mixture is stirred at room temperature for 1 h, then the solid is filtered off with suction and washed with water/methanol (1:1, 2.5 l) and acetonitrile (850 ml). The residue is dried overnight at 45° C. in the VDO to constant mass (21 h) using entraining nitrogen. A total of 1.90 kg of methyl{8-fluoro-3-[2-methoxy-5-(trifluoromethyl)phenyl]-2-oxo-1,2,3,4-tetrahydroquinazolin-4-yl}acetate are obtained as a solid, corresponding to 74.9% of theory.
Reaction SMILES: [CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Br[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].[OH-].[Na+]>[Br+].C([N+](CCCC)(CCCC)CCCC)CCC.C1C=CC=CC=1>[CH2:15]([N:12]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]2[C:13]1=[CH:1][CH:2]=[CH:3][CH:4]=2)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: c1ccc2c(c1)[nH]c1ccccc12
Reactant: CCCCCCCCCCBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br+]
Agent: [Na+]
Solvent: c1ccccc1
Product: CCCCCCCCCCn1c2ccccc2c2ccccc21
Temperature: 80 °C
Reaction time: 2 h
Yield: 88.5 %

Procedure:
To a solution of carbazole (2.1 g, 12.5 mmol), benzene (10 mL), tetrabutylammonium bromine (0.1 g, 0.7 mmol) and 1-bromodecane (3.0 mL, 15 mmol), was added 50% NaOH aqueous solution (15 mL). The solution mixture was heated to 80° C. and stirred for 2 h. The solvent was evaporated in vacuo and the residue was extracted with dichloromethane (3×30 mL). The organic layer was dried over anhydrous Na2SO4 and filtered. After removal of solvent, the product was purified by silica gel column chromatography using petroleum ether/dichloromethane as eluent affording 9-decylcarbazole as a colorless liquid (3.4 g, 90%). 1H NMR (400 MHz, CDCl3, δ) 8.10 (d, J=7.6 Hz, 2H), 7.48-7.38 (m, 4H), 7.24 (dd, J=14.4 Hz, J=1.2 Hz, 2H), 4.30 (t, J=7.2 Hz, 2H), 1.89-1.81 (m, 2H), 1.39-1.23 (m, 14H), 0.88 (t, J=7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3, δ) 140.4, 125.5, 122.8, 120.3, 118.6, 108.6, 43.1, 31.8, 29.5, 29.48, 29.40, 29.3, 28.9, 27.3, 22.7, 14.1. MS (MALDI-TOF): m/z 307.2579 (M+).
Reaction SMILES: C[O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([C:11]([F:14])([F:13])[F:12])=[CH:5][N:4]=1.Br>C(O)(=O)C>[CH3:10][O:9][C:8]1[C:3]([OH:2])=[N:4][CH:5]=[C:6]([C:11]([F:12])([F:13])[F:14])[CH:7]=1
Reactant: COc1cc(C(F)(F)F)cnc1OC
Agent: Br
Solvent: CC(=O)O
Product: COc1cc(C(F)(F)F)cnc1O
Temperature: 100 °C

Procedure:
2,3-Dimethoxy-5-(trifluoromethyl)pyridine (8.8 g, 0.042 mol) was dissolved in 30 ml of glacial acetic acid, the mixture heated to 100° C. with stirring, and 14.8 ml of 48 percent aqueous hydrobromic acid (0.13 mol) added. The mixture was allowed to react for 20 min and was then poured onto ice. The solid that formed was recovered by filtration, dried, and recrystallized from ethanol to obtain 5.5 g (67 percent of theory) of the title compound as a white powder melting at 115°-117° C. The proton nmr spectrum was consistent with the assigned structure.
Reaction SMILES: [Na].[NH3:2].[NH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10][C:11]1[C:12]([O:28][CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])=[C:13]([C:26]#[N:27])[C:14](=[C:17]([O:20][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])[C:18]=1[Cl:19])[C:15]#[N:16]>C(O)CC>[NH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10][C:11]1[C:12]([O:28][CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])=[C:13]2[C:14](=[C:17]([O:20][CH2:21][CH2:22][CH:23]([CH3:25])[CH3:24])[C:18]=1[Cl:19])[C:15](=[NH:16])[NH:27][C:26]2=[NH:2]
Reactant: CC(C)CCOc1c(Cl)c(Sc2ccccc2N)c(OCCC(C)C)c(C#N)c1C#N
Reactant: N
Agent: [Na]
Solvent: CCCO
Product: CC(C)CCOc1c(Cl)c(Sc2ccccc2N)c(OCCC(C)C)c2c1C(=N)NC2=N
Temperature: 25 °C
Reaction time: 20 h
Yield: 85.8 %

Procedure:
To a solution of sodium metal (0.7 g) in n-propyl alcohol (200 mL) was fed gaseous ammonia at a flow rate of 120 mL/min. at room temperature for 1 hour. Then, 22.8 g of 4-(2-aminophenylthio)-5-chloro-3,6-diisopentoxyphthalonitrile was added and the mixture was stirred at 50~60° C. for 20 hours. After cooling, n-propyl alcohol was distilled off and the residue was dissolved in 200 mL of toluene under warming at 30~40° C. Then, 500 mL of water was added and the mixture was stirred for dispersing and allowed to stand for phase separation. The above procedure was repeated 4 times to wash the toluene solution. The toluene was then distilled off and 200 mL of n-heptane was added. The mixture was stirred at 60~65° C. for 30 minutes and then cooled to room temperature. The resulting crystals were collected and dried to provide 20.3 g (yield 85.8%) of 5-(2-aminophenylthio)-6-chloro-1,3-diimino-4,7-diisopentoxyisoindoline. ##STR9##
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](Cl)=[C:11]([C:14]#[N:15])[N:10]([CH2:16][CH2:17][CH3:18])[C:9]2=[O:19])=[CH:4][CH:3]=1.ClC1C(OCC#C)=C[C:24]([N:31]2C(Cl)=C(C#N)N(CCC)C2=O)=C(F)C=1.[C-]#N.[K+]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:24]#[N:31])=[C:11]([C:14]#[N:15])[N:10]([CH2:16][CH2:17][CH3:18])[C:9]2=[O:19])=[CH:4][CH:3]=1
Reactant: CCCn1c(C#N)c(Cl)n(-c2ccc(Cl)cc2)c1=O
Reactant: C#CCOc1cc(-n2c(Cl)c(C#N)n(CCC)c2=O)c(F)cc1Cl
Agent: [C-]#N
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCn1c(C#N)c(C#N)n(-c2ccc(Cl)cc2)c1=O

Procedure:
The product of Example 1, 1-(4-chlorophenyl)-5-chloro-4-cyano-3-propyl-1,3-dihydro-2H-imidazol-2-one (V) (0.75 g, 2.5 mmol), was stirred in 25 mL of dimethylformamide. To this mixture was added KCN (0.5 g, 7.5 mmol) and the resulting mixture was heated to reflux for ten minutes, cooled, poured onto water, and extracted three times with 50 mL ethyl acetate. This material was then dried, filtered, and evaporated via standard techniques to give 0.38 g of 1-(4-chlorophenyl)-4,5-dicyano-3-propyl-1,3-dihydro-2H-imidazol-2-one (VI) recrystallized from ethyl acetate/hexane (m.p. 163°-5° C.).
Reaction SMILES: CC1(C)[O:6][C@@H:5]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=2)[CH2:4][O:3]1.Cl>CO.O>[C:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][C@H:5]([OH:6])[CH2:4][OH:3])=[CH:10][CH:11]=1)#[N:16]
Reactant: CC1(C)OC[C@H](COc2ccc(C#N)cc2)O1
Agent: Cl
Solvent: O
Solvent: CO
Product: N#Cc1ccc(OC[C@H](O)CO)cc1
Reaction time: 8 h
Yield: 72.1 %

Procedure:
77 g of (4S)-2,2-dimethyl-4-(4-cyanophenoxy)methyl-1,3-dioxolane, was dissolved in methanol (200 ml) and water (75 ml). Concentrated hydrochloric acid (0.5 ml) was added and the mixture was kept at 50° C. overnight. It was evaporated at reduced pressure and recrystallized from water to yield 46 g of the title compound as white leaves, m.p. 63°-65° C.
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[OH-].[Na+:7].C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O.CCCCCCCC/C=C\CCCCCC[CH2:44][C:45]([O:47][CH2:48][C@@H:49](O)[C@H]1OC[C@H](O)[C@H]1O)=[O:46].C(OC=C)(=O)C.N(C(C)(C)C#N)=NC(C)(C)C#N.[Cl-].[Na+]>CC(C)=O.O>[C:45]([O:47][CH:48]=[CH2:49])(=[O:46])[CH3:44].[C:1]([O-:5])(=[O:4])[CH:2]=[CH2:3].[Na+:7]
Reactant: C=CC(=O)O
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: O=C(O)CN(CCN(CC(=O)O)CC(=O)O)CC(=O)O
Agent: [Cl-]
Solvent: C=COC(C)=O
Solvent: O
Solvent: CC(C)=O
Product: C=CC(=O)[O-]

Procedure:
A (vinyl acetate-sodium acrylate) copolymer water-in-oil emulsion was prepared according to the following procedures: An aqueous solution was prepared by mixing, under cooling conditions, 96.49 gm of acrylic acid, 163.75 gm of water, 130 gm of a 40 percent sodium hydroxide solution and 0.02 gm of ethylenediamine tetraacetic acid. Separately, an oil solution was prepared by mixing 5.8 gm of Span-80, 113.3 gm of Isopar-M and 6.5 gm of vinyl acetate. The two solutions were combined in a high speed waring blender to give a uniform emulsion. A catalyst solution was prepared by dissolving 0.26 gm of 2,2'-azobis(isobutyronitrile) in 3.13 ml of acetone. The monomer emulsion was then deoxygenated as described in Example 1. The polymerization was carried out in the manner as in Example 1, except that a one-liter pyrex glass reactor equipped as described in Example 1, was used. The product produced was a milky white emulsion containing about 24 percent by weight of the polymer. The polymer had an intrinsic viscosity of 4.2 dl/gm as measured in a one normal aqueous sodium chloride solution.
Reaction SMILES: [Na].[C:2]([OH:21])(=[O:20])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]/[CH:10]=[CH:11]\[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[OH-].[Na+:23]>O>[C:2]([O-:21])(=[O:20])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[Na+:23]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: [Na+]
Agent: [Na]
Agent: [OH-]
Solvent: O
Product: CCCCCCCCCCCCCCCCCC(=O)[O-]

Procedure:
Solutions of the sodium salt of C8 to C16 saturated fatty acids, and of oleic acid were first prepared at about 4 percent concentration in water by neutralization of the acid with sodium hydroxide. Sodium stearate solutions were prepared directly from the solid salt. Microsuspensions were prepared to contain about 50 percent of the polymer employed in Example 3B and one percent soap by adding the amount of soap or soap solution listed in the table to 150 g of purified wet cake (about 70 percent polymer) along with the required amount of water to give 50 percent polymer solids. These were then dispersed using a Virtis Mixer (five minutes) and an Eppenbach Homogenizer (15 minutes).
Reaction SMILES: [CH3:1][O:2][N:3]1[C:8](=[O:9])[CH:7]=[CH:6][C:5]([C:10]([O:12]C)=[O:11])=[CH:4]1.C[Si](C)(C)[O-].[K+].CO>C1COCC1>[CH3:1][O:2][N:3]1[C:8](=[O:9])[CH:7]=[CH:6][C:5]([C:10]([OH:12])=[O:11])=[CH:4]1
Reactant: COC(=O)c1ccc(=O)n(OC)c1
Agent: C[Si](C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CO
Product: COn1cc(C(=O)O)ccc1=O

Procedure:
A solution of methyl 1-methoxy-6-oxo-1,6-dihydropyridine-3-carboxylate (64 mg, 0.349 mmol) and potassium trimethylsilanolate (90 mg, 0.699 mmol) in THF (6 mL) was stirred at 23° C. for 20 min. MeOH (5 mL) was added, and the mixture was filtered. The filtrate was concentrated affording 1-methoxy-6-oxo-1,6-dihydropyridine-3-carboxylic acid as a white solid.