Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O(Cl)Cl.CN(C)[CH:6]=[O:7].[CH:9]1[C:21]2[N:20]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][C:31]([N:34]5[C:46]6[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=6[C:40]6[C:35]5=[CH:36][CH:37]=[CH:38][CH:39]=6)=[CH:30][CH:29]=4)=[CH:24][CH:23]=3)[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]=2[CH:12]=[CH:11][CH:10]=1.[CH2:47]([OH:49])C.ClCCl>O>[CH:47]([C:11]1[CH:10]=[CH:9][C:21]2[N:20]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4[CH:29]=[CH:30][C:31]([N:34]5[C:46]6[CH:45]=[CH:44][C:43]([CH:6]=[O:7])=[CH:42][C:41]=6[C:40]6[C:35]5=[CH:36][CH:37]=[CH:38][CH:39]=6)=[CH:32][CH:33]=4)=[CH:24][CH:23]=3)[C:19]3[C:14]([C:13]=2[CH:12]=1)=[CH:15][CH:16]=[CH:17][CH:18]=3)=[O:49]
Reactant: c1ccc2c(c1)c1ccccc1n2-c1ccc(-c2ccc(-n3c4ccccc4c4ccccc43)cc2)cc1
Reactant: CN(C)C=O
Reactant: CCO
Agent: ClOCl
Solvent: O
Solvent: ClCCl
Product: O=Cc1ccc2c(c1)c1ccccc1n2-c1ccc(-c2ccc(-n3c4ccccc4c4cc(C=O)ccc43)cc2)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 87 %

Procedure:
Phosphosphorus oxychloride (13 ml, 21.5 g, 140 mmol) was added dropwise to a stirring mixture of N,N-dimethylformamide (5.40 ml, 5.10 g, 69.7 mmol) and 4,4′-bis(carbazol-9-yl)biphenyl (7.72 g, 16.0 mmol) and the resulting mixture was stirred at room temperature for 5 minutes then heated to 90° C. for 24 h. (nb reaction mixture was followed by TLC using 5% ethanol/dichloromethane as the eluent). The reaction mixture was poured into water (800 ml) and this beaker was placed in the ultrasonic bath for 2 hours to break up the material. The mixture was stirred for a further 2 hours then filtered. The residue was washed with water and then hexane and dried at the pump for 2 hours. The crude product, a brown solid, was heated with acetone (3×400 ml) and filtered. The product was insoluble in most organic solvent. The impurities were removed by washing with acetone. The product, 4,4′-bis(3-formylcarbazol-9-yl)biphenyl, (7.92 g, 87%) was obtained with melting point 295° C. (dec.). Found: C, 81.74; H, 4.71; and N, 4.45. C38H28N2O2. (CH3)2CO requires C, 82.25; H, 5.05; N, 4.68%). 1H n.m.r. (300 MHz, MeeSO): δ 10.09 (2H, s, CHO); 8.88 (2H, d, J 0.88 Hz, aromatic H); 8.41 (2H, d, J 7.61 Hz, aromatic H); 8.41 (4H, d, J 8.40 Hz, aromatic H); 8.00 (2H, dd, J 8.49, 1.46 Hz, aromatic H); 7.83 (4H, d, J 8.49 Hz, aromatic H); 7.38-7.61 (8H, m, aromatic H). λmax(CH2Cl2): 215 nm (ε/Lmol−1 cm−1 9163), 241 (68 488), 272 (65 928), 294 (67 194) 328 (42 620). FT-IR (solid): 3045, 2825, 2730, 1682, 1623, 1591, 1505, 1456, 1438, 1365, 1319, 1275, 1230, 1180, 802, 745 cm−1.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[CH:14]=[CH:15][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[C:17]([F:18])[C:12]3=[N:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1B(O)O>>[F:18][C:17]1[C:12]2[N:13]([C:9]([C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([C:27]4[CH:26]=[CH:25][C:24]([F:23])=[CH:29][C:28]=4[F:30])[CH:3]=3)=[CH:10][N:11]=2)[CH:14]=[CH:15][C:16]=1[C:19]([OH:22])([CH3:21])[CH3:20]
Reactant: OB(O)c1ccc(F)cc1F
Reactant: CC(C)(O)c1ccn2c(-c3ccc(F)c(Cl)c3)cnc2c1F
Product: CC(C)(O)c1ccn2c(-c3ccc(F)c(-c4ccc(F)cc4F)c3)cnc2c1F
Yield: 2 %

Procedure:
2-[3-(3-Chloro-4-fluorophenyl)-8-fluoroimidazo[1,2-α]pyridin-7-yl]-propan-2-ol and 2,4-difluorobenzeneboronic acid were coupled in the same way as in Example 30 to give 2-[8-fluoro-3-(2,2′,4′-trifluorobiphenyl-5-yl)-imidazo[1,2-α]pyridin-7-yl]propan-2-ol as an off-white solid (3 mg, 2%): δH (400 MHz, d6-DMSO) 1.56 (6H, s), 7.18-7.23 (2H, m), 7.34 (1H, t, J 8), 7.51 (1H, t, J 9), 7.61-7.69 (2H, m), 7.73-7.77 (2H, m), 8.36 (1H, dd, J 7 and 3); m/z (ES+) 401 [MH+].
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]([C:11]1[S:12][C:13]([C:16]2[C:20]([CH3:21])=[C:19]([C:22]([F:25])([F:24])[F:23])[O:18][N:17]=2)=[CH:14][CH:15]=1)=[O:10].B(Br)(Br)Br>ClCCl>[OH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]([C:11]1[S:12][C:13]([C:16]2[C:20]([CH3:21])=[C:19]([C:22]([F:25])([F:24])[F:23])[O:18][N:17]=2)=[CH:14][CH:15]=1)=[O:10]
Reactant: COc1ccccc1C(=O)c1ccc(-c2noc(C(F)(F)F)c2C)s1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: Cc1c(-c2ccc(C(=O)c3ccccc3O)s2)noc1C(F)(F)F
Temperature: 0 °C
Reaction time: 16 h
Yield: 82.1 %

Procedure:
A solution of (2-methoxyphenyl){5-[4-methyl-5-(trifluoromethyl)isoxazol-3-yl]thien-2-yl}methanone (Example 95, 37 mg, 0.1 mmol) in dichloromethane (2 mL) at −78° C. was treated with boron tribromide (100 μL of a 1 M dichloromethane solution, 0.1 mol) and allowed to warm to 0° C. and stir at that temperature for 16 h. After that time the reaction was quenched with water (3 mL) and partitioned between water (10 mL) and EtOAc (10 mL). The organic extract was washed with a brine solution (10 mL) then dried over Na2SO4, filtered, and concentrated in vacuo to afford crude product. The crude product was chromatographed on silica gel with EtOAc/hexanes (20%) as eluant to afford product as a yellow colored solid (29 mg, 82%). 1H NMR (CDCl3) 2.92 (d, J=1.8, 3H), 7.46-7.76 (m, 2H), 8.03-8.08 (m, 1H), 8.12 (d, J=4.0, 1H), 8.28 (d, J=4.0, 1H), 8.46 (dd, J=8.4, 1.8, 1H), 11.50 (s, 1H). 19F NMR −63.1.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([CH2:11][S:12][CH2:13][CH2:14][N:7]3[C@H:6]3[CH2:15][CH2:16][N:17](C(OC(C)(C)C)=O)[CH2:18][C@@H:5]23)[CH:10]=1.[CH3:26][C:27]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:28]=1B(O)O>COCCOC.C(OCC)(=O)C>[CH3:34][O:33][C:31]1[CH:30]=[CH:29][C:28]([C:2]2[CH:3]=[C:4]3[C:8]4=[C:9]([CH2:11][S:12][CH2:13][CH2:14][N:7]4[C@H:6]4[CH2:15][CH2:16][NH:17][CH2:18][C@@H:5]34)[CH:10]=2)=[C:27]([CH3:26])[CH:32]=1
Reactant: COc1ccc(B(O)O)c(C)c1
Reactant: CC(C)(C)OC(=O)N1CC[C@H]2[C@@H](C1)c1cc(Br)cc3c1N2CCSC3
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: COc1ccc(-c2cc3c4c(c2)[C@@H]2CNCC[C@@H]2N4CCSC3)c(C)c1
Temperature: 85 °C
Reaction time: 16 h
Yield: 45 %

Procedure:
To a solution of tert-butyl (7bR,11aS)-6-bromo-1,2,7b,10,11,11a-hexahydro-4H-pyrido[4,3-b][1,4]thiazepino[6,5,4-hi]indole-9(8H)-carboxylate from EXAMPLE 7, Part A (80 mg, 0.18 mmol) in 25 mL of DME (10 mL) was added 2-methyl 4 methoxyphenyl boronic acid (45 mg, 0.27 mmol) and TEA (0.26 mL, 1.8 mmol). The mixture was degassed with a stream of nitrogen for 20 min and then there was added Pd(dppf)2 (15 mg, 0.1 mmol) and the mixture was stirred at 85° C. for 16 h. The reaction was allowed to cool to ambient temperature and was diluted with ethyl acetate, washed with sat'd aqueous sodium bicarbonate and brine, dried (MgSO4), filtered through Celite and concentrated in vacuo. The residue was purified by flash chromatography (elution with hexanes/ethyl acetate) to afford (35 mg, 45% yield) of the title compound. 1H NMR (CDCl3, 300 MHz): δ 7.13 (d, 1H, J=8.1 Hz), 6.97 (s, 1H), 6.75 (m, 3H), 3.83 (s, 3H), 3.79 (m, 1H), 3.65 (m, 2H), 3.52 (m, 3H), 3.21 (m, 2H), 3.01 (m, 2H), 2.24 (s, 3H), 1.97 (m, 2H), 1.60)m, 2H), 1.21 (s, 9H). LRMS (ES+): 467 (M+H)+.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:10][C:11]1[CH:17]2[CH2:18][CH:14]([CH2:15][CH2:16]2)[C:13](=[O:19])[C:12]=1[C:20]([C:22]1[C:23]([CH3:32])=[N:24][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:27]=1)=[O:21].C(N(C(C)C)C(C)C)C>O1CCCC1>[C:1]([O:19][C:13]1[CH:14]2[CH2:18][CH:17]([C:11](=[O:10])[C:12]=1[C:20]([C:22]1[C:23]([CH3:32])=[N:24][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:26][CH:27]=1)=[O:21])[CH2:16][CH2:15]2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1nc(C(F)(F)F)ccc1C(=O)C1=C(O)C2CCC(C2)C1=O
Reactant: O=C(Cl)c1ccccc1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(C(F)(F)F)ccc1C(=O)C1=C(OC(=O)c2ccccc2)C2CCC(C2)C1=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
At 0° C., a solution of 0.562 g (0.0004 mol) of benzoyl chloride in 1 ml of tetrahydrofuran is added to a solution of 1.14 g (0.0035 mol) of 4-hydroxy-3-(2-methyl-6-trifluoromethylpyridine-3-carbonyl)bicyclo[3.2.1]oct-3-en-2-one and 0.517 g (0.004 mol) of ethyidiisopropylamine in 15 ml of tetrahydrofuran. The reaction mixture is stirred at 25° C. for 2 hours, evaporated and purified over silica gel (hexane/ethyl acetate 1:1). This gives 0.9 g (60%) of the title compound in the form of a yellowish resin. 1H NMR (CDCl3, ppm): 7.91-7.87, m, 3H; 7.64, t, J=7.5 Hz, 1 H; 7.5 0-7.40, m, 3H; 3.24, br t, J=4 Hz, 1 H; 3.14, br t, J=4 Hz, 1H; 2.70, s, 3H; 2.47, d, J=13.5 Hz, 1H; 2.40, 2.15, m, 3H; 1.95-1.8, m, 2H.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:12](=[O:15])[CH:13]=[CH2:14])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[OH:23][CH:24]([C:26]1[S:30][C:29]([CH:31]=[O:32])=[N:28][CH:27]=1)[CH3:25].C(N(CC)CC)C.O1CCCC1>[Cl-].C([N+]1C(C)=C(CCO)SC=1)C1C=CC=CC=1.C(O)C>[OH:23][CH:24]([C:26]1[S:30][C:29]([C:31](=[O:32])[CH2:14][CH2:13][C:12](=[O:15])[CH:11]([C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][CH:9]=2)[CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[N:28][CH:27]=1)[CH3:25]
Reactant: C=CC(=O)C(CC1CCOCC1)c1ccc(S(C)(=O)=O)cc1
Reactant: CC(O)c1cnc(C=O)s1
Agent: Cc1c(CCO)sc[n+]1Cc1ccccc1
Agent: [Cl-]
Solvent: CCO
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(O)c1cnc(C(=O)CCC(=O)C(CC2CCOCC2)c2ccc(S(C)(=O)=O)cc2)s1
Yield: 76.6 %

Procedure:
A mixture of 4-[4-(methylsulfonyl)phenyl]-5-(tetrahydro-2H-pyran-4-yl)pent-1-en-3-one (0.50 g), 5-(1-hydroxyethyl)-1,3-thiazole-2-carbaldehyde (0.28 g), 3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium chloride (43 mg), triethylamine (0.09 mL), tetrahydrofuran (6 mL) and ethanol (6 mL) was stirred with heating under reflux for 2 hr. The reaction mixture was concentrated, the residue was subjected to basic silica gel column chromatography, and eluted with ethyl acetate, and the fraction was concentrated. The residue was subjected to silica gel column chromatography, and the title compound (0.57 g, yield 75%) was obtained as a colorless oil from a fraction eluted with ethyl acetate. MS: 480 (MH+).
Reaction SMILES: C(O[Si:5]([CH2:14][CH2:15][CH2:16][CH3:17])([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:6][CH2:7][CH2:8][CH3:9])(=O)C.[C:18]([OH:23])(=[O:22])[C:19]([CH3:21])=[CH2:20]>>[C:18]([O:23][Si:5]([CH2:10][CH2:11][CH2:12][CH3:13])([CH2:14][CH2:15][CH2:16][CH3:17])[CH2:6][CH2:7][CH2:8][CH3:9])(=[O:22])[C:19]([CH3:21])=[CH2:20]
Reactant: CCCC[Si](CCCC)(CCCC)OC(C)=O
Reactant: C=C(C)C(=O)O
Product: C=C(C)C(=O)O[Si](CCCC)(CCCC)CCCC

Procedure:
4 g of acetoxytri-n-butylsilane and 1.33 g of commercial methacrylic acid (ATOFINA Norsocryl® MAA) are mixed at room temperature, acetic acid is then distilled under reduced pressure (45° C./13 hPa) to afford tri-n-butylsilyl methacrylate.
Reaction SMILES: C(C1C=CC=C(C(C)C)C=1N[S:14]([CH2:17][C:18](NC1N=NN(CCCCCCCCCCCC)N=1)=[O:19])(=[O:16])=[O:15])(C)C.C(C1C=CC=C(C(C)C)C=1N)(C)C.[O:51]([C:55]1[CH:61]=[C:60]([O:62][CH:63](C)C)[CH:59]=[C:58]([O:66][CH:67](C)C)[C:56]=1[NH2:57])[CH:52](C)C.[CH2:70]([SH:82])[CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH3:81]>>[CH2:70]([S:82][C:18](=[O:19])[CH2:17][S:14](=[O:16])(=[O:15])[NH:57][C:56]1[C:58]([O:66][CH3:67])=[CH:59][C:60]([O:62][CH3:63])=[CH:61][C:55]=1[O:51][CH3:52])[CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH3:81]
Reactant: CC(C)Oc1cc(OC(C)C)c(N)c(OC(C)C)c1
Reactant: CCCCCCCCCCCCn1nnc(NC(=O)CS(=O)(=O)Nc2c(C(C)C)cccc2C(C)C)n1
Reactant: CCCCCCCCCCCCS
Agent: CC(C)c1cccc(C(C)C)c1N
Product: CCCCCCCCCCCCSC(=O)CS(=O)(=O)Nc1c(OC)cc(OC)cc1OC

Procedure:
This compound was prepared in the same manner as for the title compound of Example 2, except that 2,6-diisopropylaniline was replaced with 2,4,6-triisopropoxylaniline and 2-DAT was replaced with dodecanthiol, mp 90°-93° C.
Reaction SMILES: C(O[C:4]1[C:5](=[O:14])[C:6](=[O:13])[C:7]=1[NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])C.[F:15][C:16]([F:27])([F:26])[O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][NH2:23])=[CH:20][CH:19]=1.[K+].[Br-]>>[C:9]([NH:8][C:7]1[C:6](=[O:13])[C:5](=[O:14])[C:4]=1[NH:23][CH2:22][C:21]1[CH:24]=[CH:25][C:18]([O:17][C:16]([F:15])([F:26])[F:27])=[CH:19][CH:20]=1)([CH3:10])([CH3:11])[CH3:12]
Reactant: NCc1ccc(OC(F)(F)F)cc1
Reactant: CCOc1c(NC(C)(C)C)c(=O)c1=O
Agent: [Br-]
Agent: [K+]
Product: CC(C)(C)Nc1c(NCc2ccc(OC(F)(F)F)cc2)c(=O)c1=O
Yield: 66 %

Procedure:
The title compound was prepared according to the procedure for example 1-step 2 except that 3-ethoxy-4-(tert-butylamino)-cyclobut-3-ene-1,2-dione was used in place of (R)-3-ethoxy-4-(1,2,2-trimethyl-propylamino)-cyclobut-3-ene-1,2-dione and 4-trifluoromethoxy-benzylamine was used in place of 4-fluoro-benzylamine. Yield: 66%; mp: 292°-294° C.; 1H NMR (300 MHz, DMSO-d6): δ1.36 (m, 9H), 4.73-4.79 (m 2H), 7.39 (d, J=8.0 Hz, 2H), 7.76 (d, J=8.2 Hz, 2H), 7.81 (brs, 1H), one N--H proton not seen; IR (KBr, cm-1): 3293s, 3242s, 3061w, 2980m, 1794m, 1655s, 1569s, 1542s, 1472s, 1447s, 1280-1160brs; MS (ES) m/z (relative intensity): 365 (M+ +Na, 100), 343 (M+ +H, 75); Anal. Calcd. for C16H17 F3N2O3 : C, 56.14; H, 5.01; N, 8.18. Found: C, 56.28; H, 5.05; N, 7.97.
Reaction SMILES: [CH3:1][N:2]([CH3:27])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:21]2[C:12](=[N:13][C:14]3[C:19]([N:20]=2)=[C:18]2[CH:22]=[CH:23][C:24]([NH2:26])=[CH:25][C:17]2=[CH:16][CH:15]=3)[CH:11]=[CH:10][CH:9]=1)=[O:7].[C:28](Cl)(=[O:30])[CH3:29]>>[CH3:1][N:2]([CH3:27])[CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:21]2[C:12](=[N:13][C:14]3[C:19]([N:20]=2)=[C:18]2[CH:22]=[CH:23][C:24]([NH:26][C:28](=[O:30])[CH3:29])=[CH:25][C:17]2=[CH:16][CH:15]=3)[CH:11]=[CH:10][CH:9]=1)=[O:7]
Reactant: CC(=O)Cl
Reactant: CN(C)CCNC(=O)c1cccc2nc3ccc4cc(N)ccc4c3nc12
Product: CC(=O)Nc1ccc2c(ccc3nc4cccc(C(=O)NCCN(C)C)c4nc32)c1

Procedure:
3-Acetylamino-benzo[a]phenazine-11-carboxylic acid (2-dimethylamino-ethyl)-amide was prepared in an analogous manner from 3-amino-benzo[a]phenazine-11-carboxylic acid (2-dimethylamino-ethyl)-amide and acetyl chloride;
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]2[N:7](CC3C=CC(OC)=CC=3)[C:8](=[O:15])[C:9]3[CH:10]=[CH:11][CH:12]=[N:13][C:14]=3[C:5]=2[CH:4]=1.C1(OC)C=CC=CC=1.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+]>FC(F)(F)C(O)=O>[CH3:1][O:2][C:3]1[CH:26]=[CH:25][C:6]2[NH:7][C:8](=[O:15])[C:9]3[CH:10]=[CH:11][CH:12]=[N:13][C:14]=3[C:5]=2[CH:4]=1
Reactant: COc1ccc(Cn2c(=O)c3cccnc3c3cc(OC)ccc32)cc1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: COc1ccc2[nH]c(=O)c3cccnc3c2c1
Temperature: 90 °C
Reaction time: 24 h
Yield: 78.9 %

Procedure:
9-Methoxy-6-(4-methoxybenzyl)benzo[h][1,6]naphthyridine-5(6H)-one (50 mg, 0.14 mmol) prepared in step 3 of Example 3 was dissolved in trifluoroacetic acid (5 ml), sequentially added with anisol (157 μl, 1.44 mmol) and 12N sulfuric acid (240 μl, 2.89 mmol. The mixture was stirred for one day at 90° C. The reaction mixture was cooled to room temperature and poured into a cold saturated sodium bicarbonate aqueous solution. After extraction with chloroform, the organic layer was washed with brine and dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue was washed with ethyl acetate, filtered, and dried in vacuo to obtain the title compound (25 mg, yield: 77%, white solid).
Reaction SMILES: [CH3:1][C@H]1OC(=O)C2C(O)=CC(O)=C(Cl)C=2CC(=O)C=CC=C[C@H]2O[C@H]2C1.C(O)(=O)CCCCCCC/C=C\CCCCCC.[CH:44]1([N:50]=[C:51]=[N:52][CH:53]2[CH2:58][CH2:57][CH2:56]CC2)CCCCC1>C(Cl)Cl>[CH3:1][N:50]([C:51]1[CH:56]=[CH:57][CH:58]=[CH:53][N:52]=1)[CH3:44]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: C[C@@H]1C[C@@H]2O[C@@H]2C=CC=CC(=O)Cc2c(Cl)c(O)cc(O)c2C(=O)O1
Agent: CCCCCC/C=C\CCCCCCCC(=O)O
Agent: C[C@@H]1C[C@@H]2O[C@@H]2/C=C\C=C\C(=O)Cc2c(Cl)c(O)cc(O)c2C(=O)O1
Solvent: ClCCl
Product: CN(C)c1ccccn1

Procedure:
Following a procedure similar to that described in Example 12, but using 365 mg of radicicol, 636 mg of palmitoleic acid, 20 ml of dry methylene chloride, 716 mg of dicyclohexylcarbodiimide and a catalytic amount of dimethylaminopyridine, 654 mg of the title compound were obtained.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]([O:8][CH3:9])=[O:7])[N:3]=[CH:2]1.[CH3:10][C:11]([CH3:14])([O-:13])C.[Na+].Br[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[S:25][C:26]3[C:31]([N:32]=2)=[CH:30][CH:29]=[C:28]([C:33]2([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH2:35][CH2:34]2)[N:27]=3)=[C:20]([F:42])[CH:19]=1>C(O)C>[F:42][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[C:24]1[S:25][C:26]2[C:31]([N:32]=1)=[CH:30][CH:29]=[C:28]([C:33]1([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH2:35][CH2:34]1)[N:27]=2)[CH2:17][N:1]1[CH:5]=[C:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[N:3]=[CH:2]1.[F:42][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[C:24]1[S:25][C:26]2[C:31]([N:32]=1)=[CH:30][CH:29]=[C:28]([C:33]1([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH2:35][CH2:34]1)[N:27]=2)[CH2:17][N:3]1[C:4]([C:6]([O:13][CH2:11][CH3:14])=[O:7])=[CH:5][N:1]=[CH:2]1
Reactant: CC(C)(C)[O-]
Reactant: Fc1cc(CBr)ccc1-c1nc2ccc(C3(c4ccccc4)CC3)nc2s1
Reactant: COC(=O)c1c[nH]cn1
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1cn(Cc2ccc(-c3nc4ccc(C5(c6ccccc6)CC5)nc4s3)c(F)c2)cn1
Product: CCOC(=O)c1cncn1Cc1ccc(-c2nc3ccc(C4(c5ccccc5)CC4)nc3s2)c(F)c1
Temperature: 70 °C

Procedure:
In a reactor tube was dissolved methyl 4-imidazolecarboxylate (0.047 g, 0.37 mmol) in ethyl alcohol (2 mL). To the solution was added sodium tert-butoxide (0.035 g, 0.37 mmol) followed by 2-(4-(bromomethyl)-2-fluorophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (0.081 g, 0.18 mmol) and the reaction mixture was heated to 70° C. for 1 h. The crude reaction mixture was concentrated in vacuo and purified by silica gel chromatography to afford pure ethyl 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzyl)-1H-imidazole-4-carboxylate and ethyl 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)benzyl)-1H-imidazole-5-carboxylate. MS (ESI) m/z: calculated: 498.2; Observed: 499.0.
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:4](=[O:9])[CH2:5][CH2:6][C:7]=1[CH3:8].[O:10]1[CH:15]=[CH:14][CH2:13][CH2:12][CH2:11]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[CH3:8][C:7]1[CH2:6][CH2:5][C:4](=[O:9])[C:3]=1[CH2:2][O:1][CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15][O:10]1
Reactant: CC1=C(CO)C(=O)CC1
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: O
Product: CC1=C(COC2CCCCO2)C(=O)CC1
Reaction time: 2 h
Yield: 94 %

Procedure:
2-(hydroxymethyl)-3-methyl-2-cyclopentene-1-one (2.417 g, 19.16 mmol), prepared in example 14, was dissolved in methylene chloride (60 mL). Then, dihydropyran (4.02 g 47.9 mmol) and p-toluenesulfonic acid monohydrate (36 mg, 0.19 mmol) were added at room temperature. This solution was stirred for 2 hours, and then diluted with ethyl acetate (150 mL). The solution was neutralized with a saturated sodium bicarbonate solution (150 mL), and methylene chloride (200 mL) was added for extraction. After taking the organic layer, moisture was removed with magnesium sulfate, and the solvent was removed in vacuo. Pure 3-methyl-2-[(tetrahydropyranyloxy)methyl]-2-cyclopenten-1-one was obtained by column chromatography (hexane:ethyl acetate=1:1) (yield: 94%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:9].Cl[CH2:11][C:12]#[N:13].C([O-])([O-])=O.[K+].[K+].CC(C)=O>>[NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[O:9][CH2:11][C:12]#[N:13]
Reactant: Cc1cccc(O)c1N
Reactant: N#CCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: Cc1cccc(OCC#N)c1N
Temperature: 50 °C
Yield: 50.9 %

Procedure:
Into a 1-Neck round-bottom flask was added 2-Amino-3-methyl-phenol (1.00 g, 0.00812 mol), Chloroacetonitrile (0.617 mL, 0.00974 mol), K2CO3 (1.35 g, 9.7 mmol), and Acetone (15 mL, 0.20 mol). The reaction mixture was heated at 50° C. for 4 hr, filtered and concentrated to afford title product (670 mg, 51%) LCMS 163 (M+H).
Reaction SMILES: [NH:1]1[S:6](=[O:8])(=[O:7])[NH:5][C:4]2[CH:9]=[CH:10][CH:11]=[C:12]3[CH:13]=[CH:14][CH:15]=[C:2]1[C:3]=23.[H-].[Na+].Cl[CH2:19][CH2:20][CH2:21][N:22]1[CH2:27][CH:26]=[C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:24][CH2:23]1.O>CN(C)C=O.C(OCC)(=O)C>[C:28]1([C:25]2[CH2:24][CH2:23][N:22]([CH2:21][CH2:20][CH2:19][N:1]3[S:6](=[O:8])(=[O:7])[N:5]([CH2:19][CH2:20][CH2:21][N:22]4[CH2:23][CH:24]=[C:25]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[CH2:26][CH2:27]4)[C:4]4[CH:9]=[CH:10][CH:11]=[C:12]5[CH:13]=[CH:14][CH:15]=[C:2]3[C:3]=45)[CH2:27][CH:26]=2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: ClCCCN1CC=C(c2ccccc2)CC1
Reactant: O=S1(=O)Nc2cccc3cccc(c23)N1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=S1(=O)N(CCCN2CC=C(c3ccccc3)CC2)c2cccc3cccc(c23)N1CCCN1CC=C(c2ccccc2)CC1
Temperature: 100 °C
Reaction time: 0.25 h
Yield: 19.4 %

Procedure:
A solution of 1H,3H-naphtho[1,8-cd]-1,2,6-thiadiazine 2,2-dioxide (8.8 g) in dry N,N-dimethylformamide (20 cc) is added dropwise to a suspension of sodium hydride (1.2 g, 80% suspension in oil) in N,N-dimethylformamide (50 cc). After 15 minutes' stirring, a solution of 1-(3-chloropropyl)-4-phenyl-1,2,3,6-tetrahydropyridine (9.36 g) in N,N-dimethylformamide (50 cc) is added. The reaction mixture is heated to 100° C. for 1 hour and is then cooled and poured into a mixture of water (500 cc) and ethyl acetate (300 cc). The organic phase is washed with water, is dried over magnesium sulphate and is concentrated to dryness under reduced pressure (2.7 kPa). The residue is redissolved in N,N-dimethylformamide (40 cc) and the solution is diluted with ethanol (300 cc). The precipitate is filtered off, washed with ethanol and dried and then taken up in a 0.1 N aqueous sodium hydroxide solution (200 cc) in which it partially dissolves. The mixture is filtered. The insoluble material is filtered off, washed with water and dried. After recrystallization from ethyl acetate (60 cc), 1,3-bis[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1H,3H-naphtho[1,8-cd]-1,2,6-thiadiazine 2,2-dioxide (2.38 g) is obtained, melting at 140° C. The filtrate obtained above is acidified to pH 4 with 1 N hydrochloric acid. The precipitate is redissolved in N,N-dimethylformamide (30 cc) at 100° C., the hot solution is filtered and is then diluted with ethanol (150 cc). The precipitate is filtered off, washed with ethanol (3×50 cc) and dried. 1-[3-(4-Phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1H,3H-naphtho[1,8-cd]-1,2,6-thiadiazine 2,2-dioxide (0.95 g) is obtained, melting at 240° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:20])=[O:19])=[CH:14][CH:13]=1)/[C:6]([CH3:21])=[C:5]2[CH2:22][CH2:23][O:24][NH2:25].[CH3:26][O:27][CH2:28][CH:29]=O>>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:20])=[O:19])=[CH:14][CH:13]=1)/[C:6]([CH3:21])=[C:5]2[CH2:22][CH2:23][O:24][N:25]=[CH:29][CH2:28][O:27][CH3:26]
Reactant: COCC=O
Reactant: CC1=C(CCON)c2cc(F)ccc2/C1=C\c1ccc(S(C)=O)cc1
Product: COCC=NOCCC1=C(C)/C(=C/c2ccc(S(C)=O)cc2)c2ccc(F)cc21

Procedure:
The title compound is prepared by reaction of O-2-[Z-5-fluoro-2-methyl-1-(4-methylsulfinylphenyl)methylene-1H-inden-3-yl]ethyl hydroxylamine with methoxyacetaldehyde by the method of Example 1.
Reaction SMILES: [Cl:1][CH2:2][C:3](Cl)=[O:4].[C:6]([CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)#[N:7].C([O-])([O-])=O.[Na+].[Na+].O>C(Cl)Cl>[Cl:1][CH2:2][C:3]([N:11]1[CH2:12][CH2:13][CH:8]([C:6]#[N:7])[CH2:9][CH2:10]1)=[O:4]
Reactant: N#CC1CCNCC1
Reactant: O=C(Cl)CCl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: N#CC1CCN(C(=O)CCl)CC1
Reaction time: 0.5 h

Procedure:
Chloroacetyl chloride (0.43 mL) was added to a mixture of a solution of 4-cyanopiperidine (500 mg) in CH2Cl2 (5 mL) and an aqueous 2 M Na2CO3 solution (5.7 mL) under ice-cooling, and the mixture was stirred for 30 minutes under ice-cooling. After the reaction mixture was further stirred at room temperature for 4 hours, CH2Cl2 and water were added thereto, then, extraction was performed on the mixture using CH2Cl2, and the extract was washed with saturated brine. The organic layer was dried over Na2SO4 and filtered, and the filtrate was concentrated under reduced pressure, whereby 1-(chloroacetyl)piperidine-4-carbonitrile (845 mg) was obtained as a light yellow oil.