Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[C:2]1C=CC=[C:4](C)[C:3]=1[C:9]1[N:14]=[C:13]([NH2:15])[N:12]=[C:11]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)=[CH:19][CH:18]=2)[CH:10]=1.[N:34]1C=C(B(O)O)C=[N:36][CH:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[F:32][C:30]([F:33])([F:31])[C:26]1[CH:25]=[C:24]([O:23][C:20]2[CH:19]=[CH:18][C:17]([NH:16][C:11]3[N:12]=[C:13]([NH2:15])[N:14]=[C:9]([C:3]4[CH:4]=[N:34][CH:35]=[N:36][CH:2]=4)[CH:10]=3)=[CH:22][CH:21]=2)[CH:29]=[CH:28][N:27]=1
Reactant: OB(O)c1cncnc1
Reactant: Cc1cccc(C)c1-c1cc(Nc2ccc(Oc3ccnc(C(F)(F)F)c3)cc2)nc(N)n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Nc1nc(Nc2ccc(Oc3ccnc(C(F)(F)F)c3)cc2)cc(-c2cncnc2)n1
Yield: 22.9 %

Procedure:
A suspension of 6-chloro-N4-(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl)pyrimidine-2,4-diamine (150 mg, 0.39 mmol, see example 335), pyrimidin-5-ylboronic acid (97.37 mg, 0.79 mmol), tetrakis(triphenylphosphin)palladium(0) (45.41 mg, 0.04 mmol), sodium carbonate (208.23 mg, 1.96 mmol) in 2.5 mil of anhydrous DMF was degassed for 10 min. The mixture was reacted under microwave condition at 180° C. for 20 min. The reaction mixture was filtered and concentrated. The residue was extracted with EtOAc (6 ml) and washed with 1 M NaOH solution (1 mL×2) and water (1 mL×3). The organic layer was dried to furnish 129 mg of the crude product. The crude product was purified by prep-TLC (Hex:EtOAc=2:8) to give 38 mg (23%) of the title compound as a yellow solid. 1H NMR (CD3OD): δ 9.28 (s, 2H), 9.20 (s, 1H), 8.54 (d, 1H), 7.88 (d, 2H), 7.32 (d, 1H), 7.15 (m, 3H), 6.56 (s, 1H) ppm; MS ES 426 (M+H)+, calc. 426, RT=2.35 min; TLC (Hexane:EtOAc=1:9) Rf=0.25.
Reaction SMILES: [F:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]([N:10]2[CH2:15][CH2:14][CH:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][NH2:25])=[CH:19][CH:18]=3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.C([Si]([O:45][C:46]1[CH:51]=[CH:50][CH:49]=[C:48]([O:52][CH2:53][C@@H:54]2[CH2:56][O:55]2)[CH:47]=1)(C1C=CC=CC=1)C1C=CC=CC=1)(C)(C)C>>[F:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]([N:10]2[CH2:11][CH2:12][CH:13]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([CH2:23][CH2:24][NH:25][CH2:56][C@H:54]([OH:55])[CH2:53][O:52][C:48]4[CH:49]=[CH:50][CH:51]=[C:46]([OH:45])[CH:47]=4)=[CH:21][CH:22]=3)[CH2:14][CH2:15]2)=[O:9])=[CH:4][CH:3]=1
Reactant: NCCc1ccc(NC2CCN(C(=O)NCc3ccc(F)cc3)CC2)cc1
Reactant: CC(C)(C)[Si](Oc1cccc(OC[C@@H]2CO2)c1)(c1ccccc1)c1ccccc1
Product: O=C(NCc1ccc(F)cc1)N1CCC(Nc2ccc(CCNC[C@H](O)COc3cccc(O)c3)cc2)CC1

Procedure:
4-[4-(2-Amino-ethyl)-phenylamino]-piperidine-1-carboxylic acid 4-fluoro-benzylamide (0.66 g, 1.6 mmol) was reacted tert-butyl{3-[(2S)oxiranylmethoxy] phenoxy} diphenylsilane according to Procedure G to yield the title compound (0.284 g, 0.4 mmol).
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][CH:6]([CH3:46])[CH2:7][O:8][C@@H:9]([C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([Cl:45])[CH:40]=1)[C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([NH:18][C@@H:19]([CH2:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)[CH2:20][N:21](C)[C:22](=O)OCC[Si](C)(C)C)=[O:17])[CH2:11]1)=[O:4].[C:47]([OH:53])([C:49]([F:52])([F:51])[F:50])=[O:48]>C(Cl)Cl>[C:47]([OH:53])([C:49]([F:52])([F:51])[F:50])=[O:48].[Cl:45][C:41]1[CH:40]=[C:39]([C@@H:9]([C@@H:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16](=[O:17])[NH:18][C@H:19]([CH2:20][NH:21][CH3:22])[CH2:32][CH:33]3[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]3)[CH2:11]2)[O:8][CH2:7][CH:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[CH3:46])[CH:44]=[CH:43][CH:42]=1
Reactant: COC(=O)NC(C)CO[C@@H](c1cccc(Cl)c1)[C@@H]1CCCN(C(=O)N[C@@H](CC2CCCCC2)CN(C)C(=O)OCC[Si](C)(C)C)C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CNC[C@H](CC1CCCCC1)NC(=O)N1CCC[C@@H]([C@@H](OCC(C)NC(=O)OC)c2cccc(Cl)c2)C1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A mixture of 2-(trimethylsilyl)ethyl (S)-2-((R)-3-((R)-(2-(methoxycarbonylamino)propoxy)(3-chlorophenyl)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate and TFA (2 mL) in CH2Cl2 (5 mL) was stirred at rt for 3 h. After the reaction mixture was evaporated under reduced pressure, the crude product was purified by reversed-phase HPLC to give TFA salt of methyl 1-((R)-(3-chlorophenyl)((R)-1-((S)-1-cyclohexyl-3-(methylamino)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)propan-2-ylcarbamate. MS ESI +ve m/z 539 (M+H).
Reaction SMILES: [C:1]([C:5]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:6]=1[O:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:18])[CH2:15][C:16]#[N:17])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Cl-].[NH4+].[N-:26]=[N+:27]=[N-:28].[Na+]>CN(C=O)C>[C:1]([C:5]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:6]=1[O:7][CH:8]1[CH2:9][CH2:10][N:11]([C:14](=[O:18])[CH2:15][C:16]2[NH:28][N:27]=[N:26][N:17]=2)[CH2:12][CH2:13]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)c1cc(F)ccc1OC1CCN(C(=O)CC#N)CC1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)c1cc(F)ccc1OC1CCN(C(=O)Cc2nnn[nH]2)CC1
Temperature: 25 °C
Yield: 15.2 %

Procedure:
3-[4-(2-tert-Butyl-4-fluorophenoxy)piperidin-1-yl]-3-oxopropanenitrile (400 mg, 1.26 mmol) obtained in Example 237, ammonium chloride (101 mg, 1.89 mmol) and sodium azide (123 mg, 1.89 mmol) were stirred in DMF (15 mL) at 120° C. for 16 hr. The reaction mixture was cooled to room temperature, and partitioned between ethyl acetate and water. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate 40:60-0:100) and by preparative HPLC (device: Gilson Inc., High Throughput Purification system; column: YMC Combiprep ODS-A, S-5 μm, 50×20 mm; solvent: SOLUTION A; 0.1% trifluoroacetic acid-containing water, SOLUTION B; 0.1% trifluoroacetic acid-containing acetonitrile; gradient cycle: 0.00 min (SOLUTION A/SOLUTION B=90/10), 1.00 min (SOLUTION A/SOLUTION B=90/10), 4.20 min (SOLUTION A/SOLUTION B=10/90), 5.40 min (SOLUTION A/SOLUTION B=10/90), 5.50 min (SOLUTION A/SOLUTION B=90/10), 5.60 min (SOLUTION A/SOLUTION B=90/10); flow rate: 25 mL/min; detection method: UV 220 nm) to give the title compound (69 mg, 15%).
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5]/[CH:6]=[CH:7]/[C:8]([CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([O:19][CH3:20])[CH:13]=1)=[O:9].[Na].[C:22](O)(=[O:24])C>CO>[CH3:22][O:24][CH:6]([CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])[CH2:7][C:8](=[O:9])[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([O:19][CH3:20])[CH:13]=1
Reactant: CCCCC/C=C/C(=O)CCc1ccc(O)c(OC)c1
Reactant: CC(=O)O
Agent: [Na]
Solvent: CO
Product: CCCCCC(CC(=O)CCc1ccc(O)c(OC)c1)OC
Reaction time: 4 h

Procedure:
A solution of [6]-shogaol (100 mg, 0.36 mmol) in methanol (5 mL) at 0° C. was treated with a solution of sodium (21 mg, 0.91 mmol) in methanol (1 mL). After 4.0 h, glacial acetic acid (0.5 mL) was added, and the solution was concentrated under reduced pressure. The residue was dissolved in water (5 mL), and extracted with ethyl acetate (5 mL×3). The organic phases were pooled, washed with water (5 mL×2) and brine (5 mL×1), dried over Na2SO4, and evaporated in vacuo. The residue was subjected to preparative TLC (hexane/EtOAc=4:1) to give the title compound M7 as a yellow oil (100 mg, yield 90%); 1H NMR (600 MHz, CDCl3) δ 6.69 (1H, d, J=1.6 Hz, H-2′), 6.82 (1H, d, J=8.1 Hz, H-5′), 6.66 (1H, dd, J=8.1, 1.6 Hz, H-6′), 2.75 (2H, m, H-1), 2.83 (2H, t, J=7.5 Hz, H-2), 2.64 (1H, dd, J=15.7, 7.6 Hz, H-4a), 2.40 (1H, dd, J=15.7, 4.7 Hz, H-4b), 3.66 (1H, m, H-5), 1.48 (1H, m, H-6a), 1.42 (1H, m, H-6b), 1.31-1.25 (6H, m, ranged from H-7 to H-9), 0.88 (3H, t, J=7.1 Hz, H-10), and 3.87 (3H, s, OMe-3′); positive APCIMS, m/z 309 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]3[O:19][C:20]([C:24]([O:26]CC)=[O:25])=[C:21]([CH3:23])[N:22]=3)[CH2:14][C@H:13]2[O:29][CH3:30])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].[OH-].[Li+].CO>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]3[O:19][C:20]([C:24]([OH:26])=[O:25])=[C:21]([CH3:23])[N:22]=3)[CH2:14][C@H:13]2[O:29][CH3:30])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]
Reactant: CCOC(=O)c1oc(N2CC[C@H](NC(=O)c3nc(Cl)c(CC)[nH]3)[C@H](OC)C2)nc1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CCc1[nH]c(C(=O)N[C@H]2CCN(c3nc(C)c(C(=O)O)o3)C[C@H]2OC)nc1Cl
Yield: 89.9 %

Procedure:
The same operation as in Example (91d) was performed using ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-methyl-1,3-oxazole-5-carboxylate obtained in Example (107c) (0.12 g, 0.27 mmol), 2 N lithium hydroxide (3 mL, 6 mmol), methanol (5 mL) and THF (3 mL), to obtain 0.10 g of the title compound as a colorless solid (89%).
Reaction SMILES: [CH:1]1([NH:7][C:8]([O:16][N:17]2[C:22]([CH3:24])([CH3:23])[CH2:21][CH:20]([O:25][C:26](=[O:28])[CH3:27])[CH2:19][C:18]2([CH3:30])[CH3:29])=[N:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[C:38](Cl)(=[O:40])[CH3:39]>C1(C)C=CC=CC=1>[C:38]([N:9]([CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1)[C:8]([O:16][N:17]1[C:18]([CH3:30])([CH3:29])[CH2:19][CH:20]([O:25][C:26](=[O:28])[CH3:27])[CH2:21][C:22]1([CH3:24])[CH3:23])=[N:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)(=[O:40])[CH3:39]
Reactant: CC(=O)Cl
Reactant: CC(=O)OC1CC(C)(C)N(OC(=NC2CCCCC2)NC2CCCCC2)C(C)(C)C1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CC(=O)OC1CC(C)(C)N(OC(=NC2CCCCC2)N(C(C)=O)C2CCCCC2)C(C)(C)C1
Temperature: 25 °C
Reaction time: 7 h
Yield: 22.6 %

Procedure:
To a solution of compound 1 (4.21 g, 10 mmol) [prepared according to Example 1] in toluene (25 ml) is added triethylamine (1.55 ml, 11 mmol) and acetyl chloride (0.78 ml, 11 mmol). The mixture is stirred at room temperature for 7 hours, then washed with water (2×10 ml), dried over MgSO4 and evaporated. The residue is chromatographed over silica gel with hexane-ethyl acetate (4:1) and the pure fractions are recristallized from pentane to afford 1.05 g of the title compound as a white solid, mp. 125-130° C.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH:10]3[CH2:12][CH2:11]3)=[N:6][N:5]2[C:13]=1[S:14]([N:17]=CN(CC(C)C)CC(C)C)(=[O:16])=[O:15].Cl>O1CCOCC1>[Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH:10]3[CH2:12][CH2:11]3)=[N:6][N:5]2[C:13]=1[S:14]([NH2:17])(=[O:15])=[O:16]
Reactant: CC(C)CN(C=NS(=O)(=O)c1c(Cl)nc2ccc(C3CC3)nn12)CC(C)C
Agent: Cl
Solvent: C1COCCO1
Product: NS(=O)(=O)c1c(Cl)nc2ccc(C3CC3)nn12
Temperature: 100 °C

Procedure:
N′-(2-Chloro-6-cyclopropylimidazo[1,2-b]pyridazin-3-ylsulfonyl)-N,N-diisobutylformamidine (0.93 g, 2.26 mmol) was dissolved in dioxane (9.00 mL), and 36% concentrated hydrochloric acid (9.0 mL, 107 mmol) was added dropwise to the solution under stirring at 100° C. The mixture was stirred for 15 hours at 100 to 105° C., then left to cool to room temperature and concentrated under reduced pressure until crystals occurred. Water (30.0 mL) was poured into the residues, and the crystals were completely precipitated, then filtered, washed with water and washed with methanol, to give the title compound as white crystals. The yield was 0.31 g (50.4%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:33])[C@@H:4]([NH:13][C:14]([C:16]1[CH:17]=[C:18]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=2)[CH:19]=[CH:20][C:21]=1[OH:22])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9](Br)=[CH:8][CH:7]=1.[F:34][C:35]([F:46])([F:45])[C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1>>[CH3:1][O:2][C:3](=[O:33])[C@@H:4]([NH:13][C:14]([C:16]1[CH:17]=[C:18]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=2)[CH:19]=[CH:20][C:21]=1[OH:22])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:39]2[CH:40]=[CH:41][C:36]([C:35]([F:46])([F:45])[F:34])=[CH:37][CH:38]=2)=[CH:8][CH:7]=1
Reactant: COC(=O)[C@H](Cc1ccc(Br)cc1)NC(=O)c1cc(-c2ccc(C(F)(F)F)cc2)ccc1O
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Product: COC(=O)[C@H](Cc1ccc(-c2ccc(C(F)(F)F)cc2)cc1)NC(=O)c1cc(-c2ccc(C(F)(F)F)cc2)ccc1O
Yield: 49.7 %

Procedure:
The resin-bound 3-(4-bromo-phenyl)-(2S)-[(4′-trifluoromethyl-4-hydroxy-biphenyl-3-carbonyl)-amino]-propionic acid methyl ester (50 mg, 0.1 mmol) prepared as generally described in Example 37 was reacted with 4-trifluoromethyl-phenyl boronic acid (57.2 mg, 0.3 mmol) by adapting the procedure in Example 45 to give the title compound (29.2 mg, 50%).
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:9])[CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].Cl[C:11]1[C:15]([C:16]2[CH:17]=[N:18][C:19]([CH3:22])=[CH:20][CH:21]=2)=[N:14][S:13][N:12]=1.O>C1COCC1>[CH2:3]([O:9][C:11]1[C:15]([C:16]2[CH:17]=[N:18][C:19]([CH3:22])=[CH:20][CH:21]=2)=[N:14][S:13][N:12]=1)[CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCO
Reactant: Cc1ccc(-c2nsnc2Cl)cn1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCCCCCOc1nsnc1-c1ccc(C)nc1
Reaction time: 2 h

Procedure:
Sodium hydride (0.72 g, 15 mmol) was dissolved in dry THF (20 ml) and 1-hexanol (1.53 g, 15 mmol) and a solution of 3-(3-chloro-1,2,5-thiadiazol-4-yl)-6-methylpyridine (1.06 g, 5 mmol) in dry THF (15 ml) was added. The reaction mixture was stirred for 2 h. After addition of water the mixture was extracted with ether, and the ether phase was dried and evaporated. The residue consisted of the crude title compound, which was used without further purification.
Reaction SMILES: [O:1]1[CH2:21][CH:2]1[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[C:7]([Cl:12])[C:6]=1[O:13]CC1C=CC=CC=1>C(OCC)(=O)C.[Pd]>[O:1]1[CH2:21][CH:2]1[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[C:7]([Cl:12])[C:6]=1[OH:13]
Reactant: Clc1ccc(OCC2CO2)c(OCc2ccccc2)c1Cl
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Oc1c(OCC2CO2)ccc(Cl)c1Cl
Yield: 106.3 %

Procedure:
In 140 ml of ethyl acetate, 5.595 g of 1-(2,3-epoxypropyloxy)-2-benzyloxy-3,4-dichlorobenzene is hydrogenated under atmospheric pressure using 1.65 g of 5% palladium on carbon (50% moisture) as catalyst (for 20 minutes, 625 ml of hydrogen gas is absorbed.). After the catalyst is filtered off, the filtrate is evaporated to give 4.3 g of 1-(2,3-epoxypropyloxy)-2-hydroxy-3,4-dichlorobenzene.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]([CH2:7][C:8]2[C:13]([OH:14])=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:4]([OH:15])=[CH:3][CH:2]=1.[C:16]([OH:20])(=[O:19])[CH:17]=[CH2:18]>>[C:16]([O-:20])(=[O:19])[CH:17]=[CH2:18].[CH:10]1[CH:9]=[C:8]([CH2:7][C:5]2[C:4]([OH:15])=[CH:3][CH:2]=[CH:1][CH:6]=2)[C:13]([OH:14])=[CH:12][CH:11]=1
Reactant: C=CC(=O)O
Agent: Oc1ccccc1Cc1ccccc1O
Product: C=CC(=O)[O-]

Procedure:
A bisphenol F-type epoxy resin (RE-404P, manufactured by Nippon Kayaku Co., Ltd., epoxy equivalent: 160 g/eq, hydrolyzed amount: 30 ppm) was reacted with acrylic acid of amount of 100% equivalent to epoxy groups, subjected to purification by liquid-separation treatment using ion exchanged water/toluene and then deprived of toluene by evaporation to obtain an acrylate of the bisphenol F-type epoxy resin. Thus obtained acrylate of the bisphenol F-type epoxy resin of 80 parts by weight, the Epoxy resin A of the Synthesis Example of 20 parts by weight, 3,6-bis(2-methyl-2-morphorinopropionyl)-9-n-octyl carbazole (Adeka Optmer N-1414, manufactured by Asahi Denka Kogyo Co., Ltd.) of 1.8 parts by weight, serving as a radical-forming photopolymerization initiator and an amino silane coupling agent (N-β(aminoethyl)-γ-aminopropyltrimethoxy silane, KBM-603, manufactured by Shin-Etsu Silicone Co., Ltd.) of 1.2 parts by weight were heated and dissolved at 90° C. to obtain a resin solution. Thus obtained resin solution was cooled to room temperature, then added with 4.1 parts by weight of isophthalic acid dihydrazide (trade name: IDH-S; prepared by finely grinding a material of jet-mill ground-grade manufactured by Otsuka Chemical Co., Ltd. using a jet mill; melting point: 224° C.; active hydrogen equivalent: 48.5 g/eq; average particle diameter: 1.7 μm; maximum particle diameter: 7 μm), 30 parts by weight of fused ground silica (Crystalite 1FF, manufactured by Tatsumori Co., Ltd., average particle diameter: 1.0 μm) and 1 part by weight of IXE-100 (a zirconium phosphate-series ion scavenger, manufactured by Toa Gosei Co., Ltd.), and kneaded using a three-roll mill to obtain a sealant for liquid crystals of the present invention. The sealant had viscosity of 300 Pa·s (25° C.) (measured by an R-type viscometer, manufactured by Toki Sangyo Co., Ltd.).
Reaction SMILES: [CH3:1][C:2]1[N:11]([CH:12]2[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]2=[O:19])[C:10](=[O:20])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+:21]([O-])=O)[CH:8]=2)[N:3]=1.CC#N.O>C1CCCCC=1.CN(C=O)C.[OH-].[OH-].[Pd+2]>[NH2:21][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([CH3:1])[N:11]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:10]2=[O:20]
Reactant: Cc1nc2ccc([N+](=O)[O-])cc2c(=O)n1C1CCC(=O)NC1=O
Agent: [Pd+2]
Agent: [OH-]
Solvent: O
Solvent: CC#N
Solvent: C1=CCCCC1
Product: Cc1nc2ccc(N)cc2c(=O)n1C1CCC(=O)NC1=O
Temperature: 125 °C
Reaction time: 5 h
Yield: 30.9 %

Procedure:
A suspension of 3-(2-methyl-6-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (4.1 g, 13 mmol) and 20% Pd(OH)2/C (0.9 g) in cyclohexene (20 mL) and DMF (60 mL) was heated in a 125° C. oil bath overnight. The suspension was filtered thru a pad of Celite, and washed with DMF (30 mL). The DMF solution and Charcoal (4 g) were stirred at room temperature for 5 hours. The suspension was filtered thru a pad of Celite. The solvent was removed in vacuo. To the residue, was added DMF (20 mL), and then water (80 mL) to give a suspension. The suspension was filtered and washed with water (50 mL), ethyl acetate (50 mL) and water (50 mL) to give a brown solid, which was purified with preparative HPLC (C18 5/95 for 2 minutes then gradient to 50/50 in 18 min CH3CN/H2O) to give 3-(6-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (1.15 g, 31% yield): HPLC: Waters Xterra C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% NH4HCO2, 5.31 min (99.8%); mp: 314-316° C.; 1H NMR (DMSO-d6) δ 2.08-2.14 (m, 1H, CHH), 2.54 (s, 3H, CHO, 2.55-2.67 (m, 2H, 2CHH), 2.75-2.90 (m, 1H, CHH), 5.16 (dd. J=5, 11 Hz, 1H, NCH), 5.59 (brs, 2H, NH2), 7.04-7.08 (m, 2H, Ar), 7.31-7.34 (m, 1H, Ar), 10.97 (s, 1H, NH); NMR (DMSO-d6) δ 21.06, 22.96, 30.62, 56.22, 105.89, 121.34, 122.61, 127.35, 137.89, 147.63, 149.24, 160.39, 169.68, 172.66; LCMS: MH=287; Anal Calcd for C14H14N4O3+1H2O: C, 55.26; H, 5.30; N, 18.41. Found: C, 54.99; H, 5.22; N, 18.35.
Reaction SMILES: S[C:2]1[N:11]([CH2:12][CH:13]=[CH2:14])[C:10](=[O:15])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.Cl[CH2:17][S:18][C:19]#[N:20].[H-].[Na+]>C(COC)OC>[S:18]([CH2:17][C:2]1[N:11]([CH2:12][CH:13]=[CH2:14])[C:10](=[O:15])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1)[C:19]#[N:20]
Reactant: N#CSCCl
Reactant: C=CCn1c(S)nc2ccccc2c1=O
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: C=CCn1c(CSC#N)nc2ccccc2c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of 5.8 g (0.03 mole) 2-mercapto-3-allyl-4(3H)-quinazolinone (the product of Example 5) in 200 ml dimethoxyethane, 5.4 g (0.05 mole) chloromethyl thiocyanate and 2.4 g (0.05 mole) 50% sodium hydride were added. The resulting mixture was stirred overnight at ambient temperature, refluxed at 50° C. for 8 hours, stirred overnight, refluxed at 50° C. for 8 hours and stirred overnight. The reaction mixture was washed with water, extracted with methylene chloride, dried over magnesium sulfate and stripped. The oily residue was triturated with ether, to give the above-identified product, as a solid, melting point 73°-76° C.
Reaction SMILES: [OH-].[Na+].[I-].[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:6]=1[CH2:12][CH:13]([C:19]([O:21]C)=[O:20])[CH2:14][N+](C)(C)C>CO>[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:6]=1[CH2:12][C:13](=[CH2:14])[C:19]([OH:21])=[O:20]
Reactant: COC(=O)C(Cc1c(Cl)cccc1Cl)C[N+](C)(C)C
Agent: [I-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C=C(Cc1c(Cl)cccc1Cl)C(=O)O
Yield: 112.3 %

Procedure:
Under an inert atmosphere, 120 ml of 2N sodium hydroxide were added to 53.3 g of the product of Step B in suspension in 500 ml of methanol. After refluxing the mixture for 2 hours, the solvents were eliminated under reduced pressure, and the residual aqueous phase was extracted with ether. After acidifying with 5N hydrochloric acid, extraction was done again with ether and then with ethyl acetate. The combined organic phases were dried, and the solvents were eliminated under reduced pressure to obtain 32 g of crude product which was crystallized from hexane and then melted at 132° C.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[NH:8][C:7](=S)[NH:6][C:5](=[O:10])[CH:4]=1.ClCC(O)=[O:16].[S]>O>[F:1][C:2]([F:12])([F:11])[C:3]1[NH:8][C:7](=[O:16])[NH:6][C:5](=[O:10])[CH:4]=1
Reactant: O=c1cc(C(F)(F)F)[nH]c(=S)[nH]1
Reactant: O=C(O)CCl
Agent: [S]
Solvent: O
Product: O=c1cc(C(F)(F)F)[nH]c(=O)[nH]1
Temperature: 25 °C
Reaction time: 18 h
Yield: 64.3 %

Procedure:
Compound XXVI was prepared according to the procedure of Kaiser, C. and Burger, A. J Org. Chem. 1959, 24, 113. 6-Trifluoromethyl-2-thiouracil (XXV) [Gershon, H et al. J. Het. Chem. 1983, 20(1), 219] (15 g, 76 mmol) was mixed with H2O (150 mL), chloroacetic acid (14.4 g, 152 mmol) was added and the mixture was heated to reflux. After 1 hr at reflux all the solids had dissolved. Analysis of the reaction mixture by LC-MS after 4 hrs at reflux indicated complete alkylation of the sulfur. The reaction was cooled to room temperature. Upon cooling a solid precipitated. To the mixture was added concentrated HCl (50 mL, 38%) and the mixture was heated to reflux. After 4 hrs at reflux the heat was removed, the solution cooled to room temperature and allowed to stir for 18 hrs. The solids were filtered and dried in a vacuum oven (50° C.) overnight to afford 6-trifluoromethyluracil (XXVI) as a white solid (8.8 g, 64%): m.p. 225-227° C.; 1H NMR (DMSO-d6) δ 12.1 (s, 1H), 11.6 (s, 1H), 6.1 (s, 1H); ESI/MS 179 (M−H).
Reaction SMILES: C(Cl)Cl.[SH:4][C:5]1[S:6][C:7]2[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[CH:11]=[CH:10][C:8]=2[N:9]=1.Br[CH:18]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:19]([OH:21])=[O:20]>C(N(CC)CC)C>[N+:14]([C:12]1[CH:11]=[CH:10][C:8]2[N:9]=[C:5]([S:4][CH:18]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:19]([OH:21])=[O:20])[S:6][C:7]=2[CH:13]=1)([O-:16])=[O:15]
Reactant: O=[N+]([O-])c1ccc2nc(S)sc2c1
Reactant: O=C(O)C(Br)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(O)C(Sc1nc2ccc([N+](=O)[O-])cc2s1)c1ccccc1
Yield: 18.4 %

Procedure:
A methylene chloride solution of 5.0 g (0.235 m) 2-mercapto-6-nitrobenzothiazole, 5.2 g (0.235 m) α-bromophenylacetic acid and 5.0 g (0.05 m) triethylamine is heated to gentle reflux overnight. The solution is washed twice with a dilute hydrochloric acid solution and once with water. The solution is dried over anhydrous MgSO4 and then concentrated. The residue is recrystallized once from benzene and then from acetonitrile. 1.5 g (18% yield) of title compound, having a melting point of 152°-5° C., is obtained.