Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.[OH:10][C:11]([CH2:13][O:14][C:15]1[CH:19]=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[NH:17][N:16]=1)=O.C(N(CC)CC)C>C(Cl)Cl>[O:7]1[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][NH:1][C:11]([CH2:13][O:14][C:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[NH:17][N:16]=2)=[O:10])[CH2:5][CH2:6]1
Reactant: NCCN1CCOCC1
Reactant: O=C(O)COc1cc(-c2ccccc2)[nH]n1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(COc1cc(-c2ccccc2)[nH]n1)NCCN1CCOCC1
Reaction time: 3 h

Procedure:
1.33 ml N-(2-aminoethyl)-morpholine, 2.2 g 3-hydroxycarbonylmethoxy-5-phenylpyrazole and 4.3 ml triethylamine were added in this order to 3.06 g 1-methyl-2-chloropyridinum iodide in methylene chloride. The reaction mixture was then heated to boiling for 3 hours under reflux. After cooling and washing with aqueous sodium hydroxide solution, the organic phase was evaporated, and the crude product obtained was purified chromatographically. 2.3 g 3-(2-morpholinoethylaminocarbonylmethoxy)-5-phenyl-pyrazole were obtained as an oily base. IR-spectrum (as film): 3205 cm-1, 1660 cm-1.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH:10](O)[CH:9]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:8][CH2:7]1)=[O:5])[CH3:2].OS(O)(=O)=O>C1COCC1>[CH2:1]([O:3][C:4]([N:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH:10]=[C:9]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1CCN(C(=O)OCC)c2ccccc2C1O
Agent: O=S(=O)(O)O
Solvent: C1CCOC1
Product: CCOC(=O)C1=Cc2ccccc2N(C(=O)OCC)CC1
Yield: 86.4 %

Procedure:
Compound 8 (7 g, 22.8 mmoles) was dissolved in THF (100 ml) and refluxed in presence of H2SO4 (13 ml) for 2 hours. THF was evaporated and the residue was poured in ice cooled water, extracted with ether (100 ml). The organic layer was dried (MgSO4), and evaporated. The residue was chromatographed (silica gel: 120 g, eluent: CH2Cl2 /EtOAc (95/5)] to give a viscous liquid 9 (5.7 g, 87%). (Found: C; H; N . Calc. for C16H19NO4 : C 66.42; H 6.62; N 4.84). 1H NMR (CDCl3) δ=1.1-1.5 (6H, 2 overlapped t, J=7 Hz) 2.9 (2H, t) 3.6 (2H, t) 3.9-4.4 (4H, 2 overlapped q, J=7 Hz) 7-7.5 (4H, m) 7.5-7.7 (1H, m) IR (CCl4) 2990 (m) 2950-2870 (several bands, ) 1705 (s) 1635 (m) 1605 (w) 1495 (m) 1470 (w) 1450(m) 1410 (s) 1390 (s) 1370 (m) 1340 (w) 1320 (s). Mass spectrum m/z 289.
Reaction SMILES: C(N[C:4]([NH:9][CH2:10][C:11]#C)=[N:5][CH2:6][CH2:7]S)#N.[C:13]([NH:15][C:16]([NH:21][CH2:22][CH2:23][CH2:24][C:25]#[CH:26])=[N:17][CH2:18][CH2:19][SH:20])#[N:14]>>[C:13]([NH:15][C:16]([NH:17][CH2:18][CH2:19][S:20][CH2:11][C:10]1[NH:9][CH:4]=[N:5][C:6]=1[CH3:7])=[N:21][CH2:22][CH2:23][CH2:24][C:25]#[CH:26])#[N:14]
Reactant: C#CCNC(=NCCS)NC#N
Reactant: C#CCCCNC(=NCCS)NC#N
Product: C#CCCCN=C(NC#N)NCCSCc1[nH]cnc1C

Procedure:
The general procedure of Example 1C is repeated except that the N-cyano-N'-propargyl-N"-(2-mercaptoethyl)guanidine utilized therein is replaced by an equimolar amount of N-cyano-N'-(4-pentyn-1-yl)-N"-(2-mercaptoethyl)guanidine, and the title product is thereby produced.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][C@H:12]([C:15](NC(C)C)=[O:16])[CH2:11][CH2:10]2)[C:5]([N+:21]([O-:23])=[O:22])=[CH:4][N:3]=1.N[C@@H]1CC[C@H](C(O)=[O:32])CC1>>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C@@H:9]2[CH2:10][CH2:11][C@H:12]([C:15]([OH:16])=[O:32])[CH2:13][CH2:14]2)[C:5]([N+:21]([O-:23])=[O:22])=[CH:4][N:3]=1
Reactant: CC(C)NC(=O)[C@H]1CC[C@@H](Nc2cc(Cl)ncc2[N+](=O)[O-])CC1
Reactant: N[C@H]1CC[C@@H](C(=O)O)CC1
Product: O=C(O)[C@H]1CC[C@@H](Nc2cc(Cl)ncc2[N+](=O)[O-])CC1

Procedure:
The compound was made using a procedure analogous to that used in the preparation of cis-4-(2-chloro-5-nitropyridin-4-ylamino)-N-isopropylcyclohexanecarboxamide using cis-4-aminocyclohexanecarboxylic acid.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([NH:10][C:11]3[N:16]=[C:15](Cl)[N:14]=[C:13]4[N:18]([CH3:21])[N:19]=[CH:20][C:12]=34)=[CH:9][C:4]=2[O:3][CH2:2]1.[NH:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](B2OC(C)(C)C(C)(C)O2)=[N:23]1>O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([NH:10][C:11]3[N:16]=[C:15]([C:26]4[CH:27]=[CH:28][CH:29]=[C:30]5[C:25]=4[CH:24]=[N:23][NH:22]5)[N:14]=[C:13]4[N:18]([CH3:21])[N:19]=[CH:20][C:12]=34)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: CC1(C)OB(c2n[nH]c3ccccc23)OC1(C)C
Reactant: Cn1ncc2c(Nc3ccc4c(c3)OCO4)nc(Cl)nc21
Solvent: O
Product: Cn1ncc2c(Nc3ccc4c(c3)OCO4)nc(-c3cccc4[nH]ncc34)nc21

Procedure:
Benzo[1,3]dioxol-5-yl-(6-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-amine was reacted with indazole boronic acid pinacol ester in General Procedure A. Addition of water gave a solid which was purified by preparative HPLC and trituration to give 156. NMR: (CDCl3): 3.52 (s, 3H, CH3), 4.17 (s, 3H, CH3), 6.10 (s, 2H, CH2), 6.92 (d, H, ArH, J=8.16 Hz), 7.00 (d, H, ArH, J=8.16 Hz), 7.10 (s, H, ArH), 7.16 (sbr, H, NH), 7.23 (s, H, ArH), 7.55 (t, H, ArH, J=8.17 Hz), 7.64 (d, H, ArH, J=8.31 Hz0, 8.41 (d, H, ArH, J=7.26 Hz), 9.16 (s, H, ArH), 10.20 (sbr, H, NH). MS: (ESI+) MH+=386.04
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1([CH3:16])[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]1=[O:15].[CH3:17]I.[NH4+].[Cl-]>C1COCC1>[CH3:17][N:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:13](=[O:14])[C:4]([CH3:16])([CH3:3])[C:5]1=[O:15]
Reactant: CI
Reactant: CC1(C)C(=O)Nc2ccccc2C1=O
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CN1C(=O)C(C)(C)C(=O)c2ccccc21
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 93 %

Procedure:
NaH (95% in mineral oil, 42 mg, 1.75 mmol) is added carefully to a solution of 3,3-dimethyl-1H-quinoline-2,4-dione (300 mg, 1.58 mmol) in anhydrous THF (10 mL) at 0° C. After 20 min, MeI (269 mg, 1.89 mmol) is added. The resulting mixture is stirred for overnight (˜16 h) at room temperature. Saturated NH4Cl solution is added, the mixture is extracted with ether (20 mL×3). The combined extracts are washed with brine, and dried over anhydrous Na2SO4. After concentration, the title compound is yielded (300 mg, 93% yield).
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH2:14][C:15]2[N:16]=[C:17]([C:21]3[CH:30]=[CH:29][C:24]([C:25]([O:27]C)=[O:26])=[CH:23][CH:22]=3)[O:18][C:19]=2[CH3:20])(=[O:13])=[O:12])=[CH:7][CH:6]=1)[CH3:3].[ClH:31]>>[ClH:31].[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]([S:11]([CH2:14][C:15]2[N:16]=[C:17]([C:21]3[CH:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[CH:29][CH:30]=3)[O:18][C:19]=2[CH3:20])(=[O:13])=[O:12])=[CH:9][CH:10]=1)[CH3:3]
Reactant: COC(=O)c1ccc(-c2nc(CS(=O)(=O)c3ccc(CN(C)C)cc3)c(C)o2)cc1
Agent: Cl
Product: Cc1oc(-c2ccc(C(=O)O)cc2)nc1CS(=O)(=O)c1ccc(CN(C)C)cc1
Temperature: 25 °C
Yield: 84 %

Procedure:
A solution of methyl 4-(4-((4-((dimethylamino)methyl)phenylsulfonyl)methyl)-5-methyloxazol-2-yl)benzoate (900 mg, 1.56 mmol, 1.00 equiv, 74%) in 6N hydrochloric acid (25 mL) was refluxed overnight. The resulting solution cooled to room temperature and then diluted with 30 mL of water/ice. The solid was removed by filtration out and washed with 3×20 mL of water. The filtrate and washings were combined and concentrated in vacuum to give 0.6 g (84%) of 4-(4-((4-((dimethylamino)methyl)phenylsulfonyl)methyl)-5-methyloxazol-2-yl)benzoic acid hydrochloride as a yellow solid. LC-MS: (ES, m/z): 415 [M+H]+, 395, 120.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][N:6]=1.[Br:12]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:12][CH2:1][C:2]1[S:3][C:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][N:6]=1
Reactant: CCOC(=O)c1cnc(C)s1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)c1cnc(CBr)s1
Temperature: 25 °C
Yield: 16.8 %

Procedure:
A solution of ethyl 2-methyl-5-thiazole carboxylate [S. H Mashragui, P. M. Keehn, JACS 104 4461-4465 (1982)] (4.73 g, 27.68 mmol) in carbon tetrachloride (30 ml) was treated with N-bromosuccinimide (4.92 g, 27.64 mmol) and benzoyl peroxide (0.03 g). The reaction mixture was heated to reflux under a strong light for 11/4 hours. The reaction was allowed to cool to ambient temperature and filtered. The filtrate was evaporated and subjected to chromatography (CH2Cl2) to give the title product (1.16 g, 17%). NMR (200 MH2,DMSO-d6) : δ8.4 (s, 1H) , 5.06 (s, 2H) , 4.33 (g, 2H), 1.3 (t, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-])=O)[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)=[O:4]>O1CCCC1.[Pd]>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH2:17])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)=[O:4]
Reactant: COC(=O)c1cccc(-c2cccc([N+](=O)[O-])c2)c1
Agent: [Pd]
Solvent: C1CCOC1
Product: COC(=O)c1cccc(-c2cccc(N)c2)c1
Reaction time: 8 h
Yield: 111.4 %

Procedure:
To a stirred solution of 3′-nitro-[1,1′-biphenyl]-3-carboxylic acid methyl ester (4.47 g) in anhydrous tetrahydrofuran (125 mL) under a blanket of nitrogen was added 10% palladium on activated charcoal (860 mg). The reaction was evacuated and placed under a hydrogen atmosphere and stirred overnight. The reaction mixture was filtered through Celite and the solvent was removed under reduced pressure to yield a gray oil (4.4 g). The residue was chromatographed on silica eluting with 3:1 hexane:ethyl acetate. Concentration of the appropriate fractions provided the title compound as a white solid (3.5 g).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:13]=[C:12]([OH:14])[C:11]2[C:6](=[C:7](C)[C:8]([O:15][CH3:16])=[CH:9][CH:10]=2)[N:5]=1)[CH3:2].[Br:18]C1C(OC)=CC=CC=1N>>[Br:18][C:7]1[C:8]([O:15][CH3:16])=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[C:4]([O:3][CH2:1][CH3:2])[CH:13]=[C:12]2[OH:14]
Reactant: CCOc1cc(O)c2ccc(OC)c(C)c2n1
Reactant: COc1cccc(N)c1Br
Product: CCOc1cc(O)c2ccc(OC)c(Br)c2n1

Procedure:
8-Bromo-2-ethoxy-7-methoxy-quinolin-4-ol was synthesized according to the method presented in the synthesis of 2-ethoxy-7-methoxy-8-methyl-quinolin-4-ol in example 132 with the exception of utilizing 2-bromo-3-methoxy-aniline.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:38])[C:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[NH:11][C:10]([C:21]3[CH:26]=[CH:25][C:24]([S:27]([N:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)(=[O:29])=[O:28])=[CH:23][C:22]=3[O:35][CH2:36][CH3:37])=[N:9]2)=[CH:4][CH:3]=1.[C:39](Cl)([Cl:41])=[O:40]>C(N(CC)CC)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:38])[C:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:39]([Cl:41])=[O:40])[C:10]([C:21]3[CH:26]=[CH:25][C:24]([S:27]([N:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)(=[O:28])=[O:29])=[CH:23][C:22]=3[O:35][CH2:36][CH3:37])=[N:9]2)=[CH:4][CH:3]=1
Reactant: O=C(Cl)Cl
Reactant: CCOc1cc(S(=O)(=O)N2CCCC2)ccc1C1=NC(C)(c2ccc(Cl)cc2)C(C)(c2ccc(Cl)cc2)N1
Solvent: CCN(CC)CC
Product: CCOc1cc(S(=O)(=O)N2CCCC2)ccc1C1=NC(C)(c2ccc(Cl)cc2)C(C)(c2ccc(Cl)cc2)N1C(=O)Cl

Procedure:
In a manner analogous to the method described in example 3, rac-(4S*,5R*)-4,5-bis-(4-chloro-phenyl)-2-[2-ethoxy-4-(pyrrolidine-1-sulfonyl)-phenyl]-4,5-dimethyl-4,5-dihydro-1H-imidazole (example 31) was reacted with phosgene in the presence of triethylamine to give the title compound.
Reaction SMILES: [C:1]([C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8](=[O:30])[CH2:9][N:10]([CH2:18][C:19]([N:21]1[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:22]1)=[O:20])C(=O)OC(C)(C)C)#[N:2].Cl.O1CCOCC1.CCOCC>O1CCOCC1>[CH2:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:29][N:21]1[C:19](=[O:20])[CH2:18][NH:10][CH2:9][C:8]([N:4]1[CH2:5][CH2:6][CH2:7][C@H:3]1[C:1]#[N:2])=[O:30]
Reactant: CC(C)(C)OC(=O)N(CC(=O)N1Cc2ccccc2C1)CC(=O)N1CCC[C@H]1C#N
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOCC
Product: N#C[C@@H]1CCCN1C(=O)CNCC(=O)N1Cc2ccccc2C1
Reaction time: 0.5 h
Yield: 113.2 %

Procedure:
The t-butyl (S)-[2-(cyanopyrrolidin-1-yl)-2-oxoethyl]-[2-(1,3-dihydrois oindol-2-yl)-2-oxoethyl]carbamate (280 mg) obtained above was dissolved in 1,4-dioxane (1.0 ml), and 4 N Hydrochloric acid/1,4-dioxane (1.0 ml) was added thereto and stirred for 30 minutes with ice cooling. Ether was added thereto, and precipitated crystals were collected by filtration and dried under reduced pressure to give a hydrochloride (240 mg, Y.: quant.) of the title compound.
Reaction SMILES: [CH3:1][CH:2]([CH3:6])[CH2:3][CH2:4][NH2:5].[N:7]1([CH2:13][CH:14]([N:16]2[C:29]3[CH:28]=[C:27]([C:30](=[S:32])N)[CH:26]=[CH:25][C:24]=3[S:23][C:22]3[C:17]2=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH3:15])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1>C(O)C>[CH3:1][CH:2]([CH3:6])[CH2:3][CH2:4][NH:5][C:30]([C:27]1[CH:26]=[CH:25][C:24]2[S:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]([CH:14]([CH3:15])[CH2:13][N:7]3[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]3)[C:29]=2[CH:28]=1)=[S:32]
Reactant: CC(CN1CCCCC1)N1c2ccccc2Sc2ccc(C(N)=S)cc21
Reactant: CC(C)CCN
Solvent: CCO
Product: CC(C)CCNC(=S)c1ccc2c(c1)N(C(C)CN1CCCCC1)c1ccccc1S2
Reaction time: 16 h

Procedure:
3-Methylbutylamine (4.65 cc) is added to a solution of 10-[(2RS)-1-piperidino-2-propyl]-2-phenothiazinecarbothioamide (3.07 g) in absolute ethanol (65 cc). The mixture is brought to 150° C. for 16 hours. The reaction mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 50° C. The residue is diluted with ethyl acetate (150 cc), the solution obtained is washed with distilled water (3×50 cc), dried over magnesium sulphate and then concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa), and the residue is purified by chromatography on a column (height: 23.2 cm; diameter: 3.6 cm) of silica gel (0.04-0.06 mm) with a slight excess pressure of nitrogen (40 kPa), eluting with mixtures of cyclohexane and ethyl acetate in proportions (by volume) of 80:20 (1 liter) and 50:50 (2 liters), collecting 60-cc fractions. Fractions 5 to 13 are combined and concentrated to dryness at 50° C. under reduced pressure (30 mm Hg; 4 kPa) to give N-(3-methylbutyl)-10-[(2RS)-1-piperidino-2-propyl]-2-phenothiazinecarbothioamide (2.49 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[NH:4][C:5]1[O:6][C:7]2[C:13](I)=[CH:12][CH:11]=[C:10]([O:15][CH3:16])[C:8]=2[N:9]=1.C([Sn](CCCC)(CCCC)[C:23]1[CH2:24][CH2:25][O:26][CH2:27][CH:28]=1)CCC.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>O1CCOCC1.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]>[CH3:1][O:2][C:3](=[O:17])[NH:4][C:5]1[O:6][C:7]2[C:13]([C:23]3[CH2:28][CH2:27][O:26][CH2:25][CH:24]=3)=[CH:12][CH:11]=[C:10]([O:15][CH3:16])[C:8]=2[N:9]=1
Reactant: COC(=O)Nc1nc2c(OC)ccc(I)c2o1
Reactant: CCCC[Sn](CCCC)(CCCC)C1=CCOCC1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1coc(P(c2ccco2)c2ccco2)c1
Solvent: C1COCCO1
Product: COC(=O)Nc1nc2c(OC)ccc(C3=CCOCC3)c2o1
Temperature: 100 °C
Yield: 42.3 %

Procedure:
To a stirred solution of 350 g (10.1 mmol) (7-iodo-4-methoxy-benzooxazol-2-yl)-carbamic acid methyl ester in 50 ml dioxane were added 5.63 g (15.1 mmol) tributyl-(3,6-dihydro-2H-pyran-4-yl)-stannane, 173 mg (0.30 mmol) bis(dibenzylideneacetone)palladium(0), 374 mg (1.61 mmol) tri(2-furyl)phospine. The mixture was heated at 100° C. for 22 h and then poured onto water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (2/98 methanol/dichloromethane then 5/95 methanol/dichloromethane) followed by trituration in dichloromethane afforded 1.30 g (42%) [7-(3,6-dihydro-2H-pyran-4-yl)-4-methoxy-benzooxazol-2-yl]-carbamic acid methyl ester as a white solid. ES-MS m/e (%): 305 (M+H+, 100).
Reaction SMILES: [Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[C:16]([Se:29][C:30]2[CH:40]=[CH:39][C:33]([C:34]([O:36]CC)=[O:35])=[CH:32][N:31]=2)=[CH:17][C:18]2[C:19]([CH3:28])([CH3:27])[CH2:20][CH2:21][C:22]([CH3:26])([CH3:25])[C:23]=2[CH:24]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH-].[Na+]>C1COCC1.C(O)C>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[C:16]([Se:29][C:30]2[CH:40]=[CH:39][C:33]([C:34]([OH:36])=[O:35])=[CH:32][N:31]=2)=[CH:17][C:18]2[C:19]([CH3:27])([CH3:28])[CH2:20][CH2:21][C:22]([CH3:26])([CH3:25])[C:23]=2[CH:24]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]
Reactant: CCOC(=O)c1ccc([Se]c2cc3c(cc2OCCCCCO[Si](C)(C)C(C)(C)C)C(C)(C)CCC3(C)C)nc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CC1(C)CCC(C)(C)c2cc([Se]c3ccc(C(=O)O)cn3)c(OCCCCCO[Si](C)(C)C(C)(C)C)cc21

Procedure:
In a manner similar to that of Example 2, by reaction of 312 mg (0.49 mmol) of ethyl 6-[3-[5-(tert-butyldimethylsilanyloxy)pentyloxy]-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylselanyl]nicotinate with 213 mg (5.3 mmol) of sodium hydroxide in a THF/ethanol mixture (5 ml/5 ml), 210 mg (71%) of a yellow powder are obtained. m.p.: 161° C.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@H:10]([CH3:30])[O:11][C:12]1[CH:13]=[C:14]([CH:19]=[C:20]([O:22]CC2C=CC=CC=2)[CH:21]=1)[C:15]([O:17][CH3:18])=[O:16])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>CO.[Pd]>[Si:1]([O:8][CH2:9][C@H:10]([CH3:30])[O:11][C:12]1[CH:13]=[C:14]([CH:19]=[C:20]([OH:22])[CH:21]=1)[C:15]([O:17][CH3:18])=[O:16])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: COC(=O)c1cc(OCc2ccccc2)cc(O[C@@H](C)CO[Si](C)(C)C(C)(C)C)c1
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cc(O)cc(O[C@@H](C)CO[Si](C)(C)C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 36 h
Yield: 94.5 %

Procedure:
Methyl 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[(phenylmethyl)oxy]benzoate (1000 mg, 2.33 mmol) was dissolved in methanol (30 mL) and 10% palladium on charcoal (100 mg) added. The mixture was stirred at ambient temperature for 36 h, filtered, evaporated in vacuo and chromatographed, 0-100% ethyl acetate in isohexane, to give methyl 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-hydroxybenzoate (750 mg). The material was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[OH:11].Br[CH2:13][CH2:14][Cl:15].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH2:13][CH2:14][Cl:15]
Reactant: ClCCBr
Reactant: O=[N+]([O-])c1ccc(Cl)c(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=[N+]([O-])c1ccc(Cl)c(OCCCl)c1
Temperature: 80 °C

Procedure:
A mixture of 2-chloro-5-nitrophenol (4 g, 23 mmol), 1-bromo-2-chloroethane (9 mL, 115 mmol), and K2CO3 (8 g, 58 mmol) in DMF (50 mL) was heated at 80° C. for 18 h. The mixture was diluted with water and extracted several times with EtOAc. The combined organic layers were washed with 1N NaOH (aq) and concentrated in vacuo to yield the title compound and a bromo adduct contaminant.
Reaction SMILES: C[O-].[Na+].CO.[CH:6](=O)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:27][N:28]1[CH:33]=[CH:32][C:31]([C:34]([O:36]C)=[O:35])=[CH:30][C:29]1=[NH2+:38]>O>[C:7]1([C:6]2[N:38]=[C:29]3[CH:30]=[C:31]([C:34]([OH:36])=[O:35])[CH:32]=[CH:33][N:28]3[N:27]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: O=Cc1ccccc1
Reactant: COC(=O)c1ccn(N)c(=[NH2+])c1
Agent: C[O-]
Agent: Cc1cc(C)c(S(=O)(=O)[O-])c(C)c1
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=C(O)c1ccn2nc(-c3ccccc3)nc2c1
Reaction time: 1 h

Procedure:
Sodium methoxide (10.9 ml, a 5 M methanol solution) and benzaldehyde (3.3 ml) were added to a methanol (100 ml) solution of the 1-amino-4-(methoxycarbonyl)pyridin-2(1H)-iminium 2,4,6-trimethylbenzenesulfonate (10 g) obtained in (Example 3.18) <Step 3>, and the obtained mixture was then stirred for 1 hour. Thereafter, water (5 ml) was added to the reaction solution, and the mixed solution was then stirred at 40° C. for 30 minutes. Thereafter, methanol was distilled away under reduced pressure, water (50 ml) and methyl tert-butyl ether (50 ml) were then added to the residue, followed by stirring the mixture. An organic layer was separated from a water layer, and the water layer was then washed with methyl tert-butyl ether (50 ml) again. The water layer was adjusted to pH 4 by addition of 4 N hydrochloric acid (10 ml), and a mixed solution of methylene chloride and methanol (95:5, 50 ml) was then added thereto. Insoluble substances were removed by filtration, and an organic layer was then separated from a water layer. The water layer was extracted with a mixed solution of methylene chloride and methanol (95:5, 50 ml) twice. Organic layers were then combined, and the solvent was then distilled away under reduced pressure. The obtained residue was successively triturated with methyl tert-butyl ether (50 ml) and methanol (50 ml). The obtained solid was washed with methanol (20 ml), and was then dried at 50° C. under reduced pressure, so as to obtain the title compound (3.2 g) in the form of a brown solid.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:9]([C:25](Cl)=[O:26])[CH2:10][CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][O:21][CH2:22][CH3:23])=[CH:15][C:14]=2[CH3:24])=[N:4][CH:5]=[N:6][C:7]=1[CH3:8].[CH3:28][NH2:29]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:3]([N:9]([CH2:10][CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][O:21][CH2:22][CH3:23])=[CH:15][C:14]=2[CH3:24])[C:25](=[O:26])[NH:29][CH3:28])=[N:4][CH:5]=[N:6][C:7]=1[CH3:8]
Reactant: CCOCCc1ccc(OCCN(C(=O)Cl)c2ncnc(C)c2Cl)c(C)c1
Reactant: CN
Solvent: Cc1ccccc1
Product: CCOCCc1ccc(OCCN(C(=O)NC)c2ncnc(C)c2Cl)c(C)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Into a solution of 1.0 g of 5-chloro-N-chlorocarbonyl-N-{2-[4-(2-ethoxyethyl)-2-methylphenoxy]ethyl}-6-methyl-4-pyrimidine amine dissolved in 20 ml of toluene was added under stirring 1 ml of an aqueous 40% monomethylamine solution, and the mixture was stirred at room temperature for one hour.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([S:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:5][N:6]=1.[OH:14][CH:15]=[C:16]([CH3:22])[C:17](OCC)=O>>[C:8]1([S:7][C:4]2[S:3][C:2]3=[N:1][CH:17]=[C:16]([CH3:22])[C:15](=[O:14])[N:6]3[N:5]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CCOC(=O)C(C)=CO
Reactant: Nc1nnc(Sc2ccccc2)s1
Product: Cc1cnc2sc(Sc3ccccc3)nn2c1=O
Yield: 58 %

Procedure:
Seven point two (7.2) g of the thus obtained 2-amino-5-phenylthio-1,3,4-thiadiazole and 4.9 g of ethyl 3-hydroxy-2-methyl-2-propenoate were mixed with 13 g of polyphosphoric acid. By the same procedure as in Preparation Example 2, 5.9 g of 2-phenylthio-6-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one was obtained m.p. 141°~143° C. Yield 58%.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1/[CH:7]=[CH:8]/[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C([O-])=O.[NH4+].C(OCC)(=O)C>C(O)C.O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10]
Reactant: CC(C)(C)OC(=O)/C=C/c1ccccn1
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)CCc1ccccn1
Yield: 89.3 %

Procedure:
tert-Butyl (E)-3-(2-pyridyl)-2-propenoate (1.1 g, 5.4 mmol) was dissolved in ethanol (12 ml), and a solution of ammonium formate (2.0 g, 32.0 mmol) in water (3 ml) was added thereto. The reaction mixture was refluxed for 1.5 hrs, combined with ethyl acetate and water and filtered. The filtrate was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the titled compound (1.0 g, 94%).
Reaction SMILES: [CH:1]1[C:6]([NH2:7])=[CH:5][CH:4]=[C:3]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)[CH:2]=1.[N:16]1[N:17]=[CH:18][N:19]([C:21]2[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=2)[CH:20]=1>>[NH:8]([C:3]1[CH:2]=[CH:1][C:6]([NH:7][C:25](=[O:26])[C:24]2[CH:28]=[CH:29][C:21]([N:19]3[CH:18]=[N:17][N:16]=[CH:20]3)=[CH:22][CH:23]=2)=[CH:5][CH:4]=1)[C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:25](=[O:26])[C:24]2[CH:23]=[CH:22][C:21]([N:19]3[CH:20]=[N:16][N:17]=[CH:18]3)=[CH:29][CH:28]=2)=[CH:11][CH:10]=1
Reactant: O=C(O)c1ccc(-n2cnnc2)cc1
Reactant: Nc1ccc(Nc2ccc(N)cc2)cc1
Product: O=C(Nc1ccc(Nc2ccc(NC(=O)c3ccc(-n4cnnc4)cc3)cc2)cc1)c1ccc(-n2cnnc2)cc1

Procedure:
Compound 747 was prepared according to the procedure described in Scheme IV from 4,4′-diaminodiphenylamine and 4-(4H-1,2,4-triazol-4-yl)benzoic acid. [M+H]+ calcd for C30H23N9O2: 542.20; found 541.99.