Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:7][C@H:6]([OH:8])[C@@H:5]([CH:9]([CH3:11])[CH3:10])[CH2:4][CH2:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O/[N:32]=[C:33](/[C:39](=[O:41])[CH3:40])\[C:34]([O:36][CH2:37][CH3:38])=[O:35].N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[CH3:1][C@@H:2]1[CH2:7][C@@H:6]([O:8]/[N:32]=[C:33](/[C:39](=[O:41])[CH3:40])\[C:34]([O:36][CH2:37][CH3:38])=[O:35])[C@@H:5]([CH:9]([CH3:11])[CH3:10])[CH2:4][CH2:3]1
Reactant: CC(C)[C@H]1CC[C@H](C)C[C@@H]1O
Reactant: CCOC(=O)/C(=N\O)C(C)=O
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCOC(=O)/C(=N\O[C@@H]1C[C@@H](C)CC[C@@H]1C(C)C)C(C)=O
Yield: 14 %

Procedure:
(1S, 2R, 5S)-(+)-Menthol (7.03 g, 45 mmol), triphenylphosphine (8.65 g, 33 mmol), ethyl (Z)-2-hydroxyimino-3-oxobutyrate (4.77 g, 33 mmol) and diethyl azodicarboxylate (5.7 g, 33 mmol) were reacted by analogy with Example 4a Method 3 to give the title compound (1.37 g, 14%), νmax (CH2Cl2) 2960, 2930, 2870, 1745, 1690, 1370, 1320, 1235, 1075, and 1010cm-1 ; δH (400 MHz, CDCl3) 0.87 (3H, d, J 6.6 Hz), 0.90 (3H, d, J 6.8 Hz), 0.92 (3H, d, J 6.7 Hz), ca 0.9 (1H, m), 1.02-1.12 (2H, m), 1.1-1.3 (1H, m), 1.32 (3H, t, J 7.1 Hz), 1.50-1.65 (2H, m), 1.67-1.78 (2H, m), 2.06-2.18 (1H, m), 2.40 (1H, s), 4.34 (2H, dq, J 7.1 and 1.0 Hz), and 4.70 (1H, broad s); δ13C (100 MHz, CDCl3), 14.24 (CH3), 20.70 (CH3), 20.97 (CH3), 22.26 (CH3) 25.04 (CH2), 25.11 (CH3) 26.06 (CH), 29.10 (CH), 34.77 (CH2), 39.44 (CH2) 46.98 (CH), 61.70 (CH2), 83.43 (CH), 150.28, 161.53, 192.94 [Ammonia CI mass spectrum Found: MH+ (298); MNH+ (315)].
Reaction SMILES: C([O-])([O-])=O.[Cs+].[Cs+].[CH2:7]([O:14][C:15](=[O:35])[NH:16][CH:17]1[CH2:29][C:28]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([O:30][C:31]([F:34])([F:33])[F:32])[CH:26]=3)[NH:21][C:20]=2[CH2:19][CH2:18]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Br[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[N:39]=1>CN(C=O)C.CCOC(C)=O>[CH2:7]([O:14][C:15](=[O:35])[NH:16][CH:17]1[CH2:29][C:28]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([O:30][C:31]([F:34])([F:32])[F:33])[CH:26]=3)[N:21]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[N:39]=3)[C:20]=2[CH2:19][CH2:18]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: O=C(NC1CCc2[nH]c3ccc(OC(F)(F)F)cc3c2C1)OCc1ccccc1
Reactant: Fc1cccc(CBr)n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(NC1CCc2c(c3cc(OC(F)(F)F)ccc3n2Cc2cccc(F)n2)C1)OCc1ccccc1
Temperature: 50 °C
Yield: 56.2 %

Procedure:
Add Cs2CO3 (6.44 g, 19.8 mmol) to a solution of (6-trifluoromethoxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-carbamic acid benzyl ester (Preparation 43) (4.00 g, 9.88 mmol) and 2-bromomethyl-6-fluoropyridine (Preparation 44) (3.11 g, 13.8 mmol) in DMF (40 mL). Heat the resulting mixture to 50° C. for 18 h and then dilute with EtOAc (120 mL). Wash the organics with water (3×40 mL), dry (MgSO4), filter, and concentrate to give the crude product (5.40 g) as a brown oil. Purify the crude product on silica gel (120 g) eluting with 2545% EtOAc/hexanes to afford 2.85 g (56%) of the title compound as a tan oil. MS (ES): m/z 514 (M+1); HPLC (Method A): Rt=4.54 min (95%).
Reaction SMILES: CN(C)S([N:6]1[C:10]([CH3:11])=[C:9]([CH2:12][CH:13]2[C:25](=[O:26])[C:24]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[N:17]([CH3:27])[C:16]=3[CH2:15][CH2:14]2)[N:8]=[CH:7]1)(=O)=O>Cl.C(O)C>[CH3:27][N:17]1[C:16]2[CH2:15][CH2:14][CH:13]([CH2:12][C:9]3[N:8]=[CH:7][NH:6][C:10]=3[CH3:11])[C:25](=[O:26])[C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2
Reactant: Cc1c(CC2CCc3c(c4ccccc4n3C)C2=O)ncn1S(=O)(=O)N(C)C
Agent: Cl
Solvent: CCO
Product: Cc1[nH]cnc1CC1CCc2c(c3ccccc3n2C)C1=O
Yield: 89.1 %

Procedure:
A solution of N,N,5-trimethyl-4-[(2,3,4,9-tetrahydro-9-methyl-4-oxo -1H-carbazol-3-yl)methyl]-1H-imidazole-1-sulphonamide (400 mg) in 2 N hydrochloric acid (30 ml) and absolute ethanol (5 ml) was heated at 100°-110° for 8 h. Work up and FCC as described in Example 32 gave the title compound (261 mg) as a solid. The 1H-n.m.r. and t.l.c. of this material were consistent with those obtained for the product of Example 8.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C:10]1=[O:15].[Br:16]Br>C(Cl)(Cl)Cl>[Br:16][CH:11]1[CH2:12][CH2:13][CH2:14][CH:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[C:10]1=[O:15]
Reactant: BrBr
Reactant: O=C1CCCCC1c1ccc(Cl)cc1Cl
Solvent: ClC(Cl)Cl
Product: O=C1C(Br)CCCC1c1ccc(Cl)cc1Cl
Temperature: 25 °C
Yield: 116.8 %

Procedure:
2-(2,4-Dichloro-phenyl)-cyclohexanone (50 mg, 0.21 mmol) was dissolved in chloroform (1 mL). To this solution bromine (34.5 mg, 0.22 mmol) in chloroform (0.5 mL) was added drop wise at room temperature. The reaction was stirred for 1½ hours at room temperature. The solvent was removed under reduced pressure to yield the crude title compound (79 mg) which was used directly in the next step without further purification.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH3:9])[CH:5]=[C:6]([CH3:8])[CH:7]=1.[CH:10]1([SH:16])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C([O-])([O-])=O.[K+].[K+].C(O)CO>[Cu]I.CC(O)C>[CH3:8][C:6]1[CH:7]=[C:2]([S:16][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:3]=[C:4]([CH3:9])[CH:5]=1
Reactant: Cc1cc(C)cc(I)c1
Reactant: SC1CCCCC1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: OCCO
Product: Cc1cc(C)cc(SC2CCCCC2)c1
Yield: 70.8 %

Procedure:
The general procedure in example 39 was followed. 5-Iodo-m-Xylene (144 μL, 1.0 mmol), cyclohexylmercaptan (122 μL, 1.0 mmol), CuI (10 mg, 0.05 mmol), K2CO3 (276 mg, 2.0 mmol), ethylene glycol (111 μL, 2.0 mmol) and 2-propanol (1.0 mL) were used to obtain the cyclohexyl 3,5-dimethylphenyl sulfide (156 mg, 71% yield) as colorless oil. Column chromatographic solvent (hexane). Rf=0.4 (hexane). 1H NMR (CDCl3, 300 MHz) δ 6.99 (s, 2 H), 6.82 (s, 1 H), 3.02-3.10 (m, 1 H), 2.28 (s, 6 H), 1.96-2.00 (m, 2 H), 1.74-1.77 (m, 2 H), 1.56-1.63 (m, 1 H), 1.21-1.42 (m, 4 H). 13C NMR (CDCl3, 75 MHz) δ 138.4, 134.7, 129.7, 128.7, 46.8, 33.8, 26.5, 26.2, 21.6. IR (neat, cm−1) 3088, 3060, 3012, 2962, 2867. MS (EI) m/z (relative intensity) 220 (40), 138 (100), 105 (30). Anal Cald for C14H20S, Cald. C: 76.30, H: 9.15; Found C: 76.30, H: 9.17.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:32](Cl)=[O:33])[C:13]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)([CH3:24])[C:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH3:36])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[CH3:39][S:40]([CH2:43][CH2:44][CH2:45][N:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1)(=[O:42])=[O:41]>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:49]3[CH2:48][CH2:47][N:46]([CH2:45][CH2:44][CH2:43][S:40]([CH3:39])(=[O:41])=[O:42])[CH2:51][CH2:50]3)=[O:33])[C@@:13]([C:25]3[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH3:36])[CH:6]=1)([CH3:2])([CH3:4])[CH3:3]
Reactant: COc1cc(C(C)(C)C)ccc1C1=NC(C)(c2ccc(Cl)cc2)C(C)(c2ccc(Cl)cc2)N1C(=O)Cl
Reactant: CS(=O)(=O)CCCN1CCNCC1
Agent: Cl
Product: COc1cc(C(C)(C)C)ccc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(CCCS(C)(=O)=O)CC1

Procedure:
In a manner analogous to the method described in example 5, rac-(4S*,5R*)-2-(4-tert-butyl-2-methoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride was reacted with 1-(3-methanesulfonyl-propyl)-piperazine dihydrochloride (prepared as described in Fotouhi, N. et al. WO 2005110996) to give the title compound as a racemic mixture. The enantiomers were separated by supercritical fluid chromatography (Berger Instrument Multi-Gram II, Daicel ChiralPak OD-H 3×25 cm, 35° C. at 100 bar, eluting with 35% methanol in carbon dioxide) gave the title compound. HR-MS (ES, m/z) calculated for C37H47N4O4SCl2 [(M+H)+] 713.2690, observed 713.2690.
Reaction SMILES: Cl.[NH2:2][OH:3].C(=O)([O-])O.[Na+].[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][C:21]1[N:26]=[C:25]([C:27]#[N:28])[CH:24]=[CH:23][CH:22]=1)[C:15]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[CH:14]2.O>CS(C)=O>[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][C:21]1[N:26]=[C:25]([C:27](=[N:2][OH:3])[NH2:28])[CH:24]=[CH:23][CH:22]=1)[C:15]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[CH:14]2
Reactant: NO
Reactant: COc1ccc2c(c1)cc(-c1ccccc1)n2Cc1cccc(C#N)n1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: COc1ccc2c(c1)cc(-c1ccccc1)n2Cc1cccc(C(N)=NO)n1
Temperature: 50 °C
Reaction time: 1 h
Yield: 99.1 %

Procedure:
To a suspension of hydroxylamine hydrochloride (233 mg) in dimethylsulfoxide (1.7 mL) was added sodium hydrogen carbonate (338 mg), and this mixture was stirred at 50° C. for 1 hour. Subsequently, 6-(5-methoxy-2-phenylindol-1-ylmethyl)pyridine-2-carbonitrile (114 mg) was added thereto, followed by stirring at 80° C. overnight. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain the title compound (124 mg). 1H-NMR (DMSO-d6) δ ppm: 3.76 (3H, s), 5.51 (2H, s), 5.65 (2H, br s), 6.59 (1H, s), 6.70-6.85 (2H, m), 7.11 (1H, d, J=2.4 Hz), 7.32 (1H, d, J=8.9 Hz), 7.35-7.70 (7H, m), 9.92 (1H, s).
Reaction SMILES: Cl.[CH2:2]([O:9][C:10]([C:12]1[S:13][C:14]2[CH:21]=[CH:20][C:19]([NH:22]N)=[CH:18][C:15]=2[C:16]=1[CH3:17])=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.O.Cl.[NH:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1>C(O)(C)C>[CH2:2]([O:9][C:10]([C:12]1[S:13][C:14]2[C:15](=[C:18]3[C:19](=[CH:20][CH:21]=2)[NH:22][C:29]2[CH2:30][CH2:31][NH:26][CH2:27][C:28]3=2)[C:16]=1[CH3:17])=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: Cc1c(C(=O)OCc2ccccc2)sc2ccc(NN)cc12
Reactant: O=C1CCNCC1
Agent: Cl
Solvent: CC(C)O
Solvent: O
Product: Cc1c(C(=O)OCc2ccccc2)sc2ccc3[nH]c4c(c3c12)CNCC4

Procedure:
1 g of 5-hydrazino-3-methylbenzothiophene-2-carboxylic acid benzyl ester hydrochloride and 1 g of 4-piperidone hydrochloride monohydrate are boiled in 50 ml of isopropanol under N2 for 10 hours. The solvent is then evaporated off, the residue is suspended in water and the aqueous suspension is rendered alkaline with KHCO3 and extracted with ethyl acetate; the extract is washed, dried and evaporated and the residue is recrystallised from isopropanol. Melting point 178° C.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[CH:15][C:11]3[O:12][CH2:13][O:14][C:10]=3[CH:9]=2)[C:5]([C:17]#[N:18])=[C:4]([S:19]([CH3:22])(=O)=O)[N:3]=1.C(S)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[CH:15][C:11]3[O:12][CH2:13][O:14][C:10]=3[CH:9]=2)[C:5]([C:17]#[N:18])=[C:4]([S:19][CH2:22][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:3]=1
Reactant: SCc1ccccc1
Reactant: CS(=O)(=O)c1nc(N)nc(-c2ccc3c(c2)OCO3)c1C#N
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: N#Cc1c(SCc2ccccc2)nc(N)nc1-c1ccc2c(c1)OCO2

Procedure:
From 2-amino-4-benzo[1,3]dioxol-5-yl-6-methanesulfonyl-pyrimidine-5-carbonitrile, benzyl mercaptan and DBU in DME. ES-MS m/e (%): 401 (M+K+, 30), 385 (M+Na+, 24), 363 (M+H+, 100).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])[CH:5]=[CH:6][CH:7]=1.S(=O)(=O)(O)O.[CH2:18](O)[CH3:19]>>[CH2:18]([O:11][C:10](=[O:12])[CH2:9][CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([OH:1])[CH:3]=1)[CH3:19]
Reactant: O=C(O)CCc1cccc(O)c1
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)CCc1cccc(O)c1

Procedure:
To a solution of commercially available 3-(3-hydroxy-phenyl)-propionic acid (25 g, 150.4 mmol) in ethanol (250 mL) was added concentrated sulfuric acid (3.0 mL). The solution was heated to reflux overnight. The solvent was removed in vacuo, and the resulting oil was diluted ethyl acetate and placed in a separatory funnel. The organic portion was extracted 2× with 5% NaHCO3 and once with brine. The solution was dried (MgSO4), filtered and concentrated to a dark tan oil (30 g). This material was carried on to the next step without further purification.
Reaction SMILES: C1(C)C=CC(S(O[CH2:11][CH:12]2[S:24][C:16]3=[N:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[N:15]3[CH2:14][CH2:13]2)(=O)=O)=CC=1.[CH2:26]([NH2:30])[CH2:27][CH2:28][CH3:29].[H-].[Na+].O>C(Cl)(Cl)Cl>[CH2:26]([NH:30][CH2:11][CH:12]1[S:24][C:16]2=[N:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:15]2[CH2:14][CH2:13]1)[CH2:27][CH2:28][CH3:29]
Reactant: Cc1ccc(S(=O)(=O)OCC2CCn3c(nc4ccccc43)S2)cc1
Reactant: CCCCN
Agent: [H-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: O
Product: CCCCNCC1CCn2c(nc3ccccc32)S1
Yield: 43.3 %

Procedure:
To a solution of 2.24 g of 3,4-dihydro-2-p-toluenesulfonyloxymethyl-2H-(1,3)-thiazino[3,2-a]benzimidazole in chloroform (30 ml) was added 4 ml of n-butylamine. A catalytic amount of sodium hydride was thereafter added under ice-cooling, stirring conditions. After stirring for 15 minutes at room temperature, the mixture was refluxed for 24 hours. The reaction mixture was cooled and then condensed under reduced pressure. The residue was added with water and extracted with chloroform. The extract was washed with water, dried over anhydrous magnesium sulfate. Chloroform was evaporated under reduced pressure. The residue was chromatographed on silica gel and eluted with chloroform to obtain 0.71 g (yield: 43.3%) of the intended product, m.p. 122°-124° C.; IR νmaxKBr cm-1 : 3320, 3100-2700, 1430; Anal. Calcd. for C15H21N3S: C, 65.42; N, 7.68; N, 15.26; S, 11.64; Found C, 65.63; H, 7.61; N, 15.46; S, 11.30.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[C:19]([C:20]2[N:21]([C:29]3[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:31][CH:30]=3)[CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[N:24]=2)=[CH:18][CH:17]=[CH:16][N:15]=1.I[CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42]>C1COCC1>[CH3:13][C:14]1[C:19]([C:20]2[N:21]([C:29]3[CH:34]=[CH:33][C:32]([S:35]([CH2:38][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])(=[O:37])=[O:36])=[CH:31][CH:30]=3)[CH:22]=[C:23]([C:25]([F:27])([F:28])[F:26])[N:24]=2)=[CH:18][CH:17]=[CH:16][N:15]=1
Reactant: C[Si](C)(C)CI
Reactant: Cc1ncccc1-c1nc(C(F)(F)F)cn1-c1ccc(S(C)(=O)=O)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: Cc1ncccc1-c1nc(C(F)(F)F)cn1-c1ccc(S(=O)(=O)CC[Si](C)(C)C)cc1
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 73.2 %

Procedure:
To a solution of diisopropylamine (0.7 mL, 0.005 mol) in 9 mL of dry THF was added butyllithium (BuLi) (2.83 mL of 1.62M solution in hexane, 4.6 mmol) at 0° C. The solution was stirred at this temperature for 5 minutes and cooled to -78° C. with a dry ice/isopropanol bath. A solution of 2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine (Example 46) (1.46 g, 3.8 mmol) in 12 mL of dry THF was added over 10 minutes and the reaction mixture was stirred at -78° C. for 1 hour. (Iodomethyl)trimethylsilane (1.23 g, 57 mmol) was added dropwise and the reaction mixture was warmed to room temperature and was stirred overnight. The reaction was quenched with 50 mL of 1N HCl and the aqueous phase was extracted with ethyl acetate (3×60 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude mixture was purified by chromatography on silica gel (ethyl acetate/hexane, 65:35) to give 1.30 g of 2-methyl-3-[1-[4-[[2-(trimethylsilyl) ethyl]sulfonyl]phenyl]-4-(trifluoromethyl) -1H-imidazol-2-yl]pyridine as a white solid (74%): mp(DSC) 155°-157° C. Anal. Calc'd. for C21H24F3N3O2SSi: C, 53.94; H, 5.17; N, 8.99; S, 6.86. Found: C, 53.77; H, 4.94; N, 8.75; 6.98.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[C:6]([OH:11])[CH:5]=1.[Cl:13][C:14]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:15]=1[CH:16]=O>CO>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]2[N:10]=[C:16]([C:15]3[C:14]([Cl:13])=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:22])[O:11][C:6]=2[CH:5]=1)=[O:12]
Reactant: COC(=O)c1ccc(N)c(O)c1
Reactant: O=Cc1c(Cl)cccc1Cl
Solvent: CO
Product: COC(=O)c1ccc2nc(-c3c(Cl)cccc3Cl)oc2c1
Temperature: 45 °C
Reaction time: 1 h

Procedure:
To a solution of 4-amino-3-hydroxy-benzoic acid methyl ester (2.0 g) in MeOH (100 mL) was added 2,6-dichlorobenzaldehyde (2.1 g). The reaction mixture was heated at 45° C. overnight, and then concentrated in vacuo. The residue was dissolved in THF (10 mL) and dichloromethane (90 mL). To the mixture solution was added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (2.72 g). The reaction mixture was stirred for 1 h, diluted with NaHCO3 aqueous solution, extracted with EtOAc, and washed with brine. The extracts were dried over Na2SO4 and concentrated in vacuo. Purification by column chromatography (SiO2, 2:3 EtOAc/Hexane) gave 2-(2,6-dichlorophenyl)-benzooxazole-6-carboxylic acid methyl ester: MS (m/z) 321.9 (M+1).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=2[Cl:23])=[CH:4][CH:3]=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[C:14]([Cl:23])=[CH:15][C:16]([NH2:20])=[CH:17][C:18]=2[Cl:19])=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1
Solvent: Cc1ccccc1
Product: Nc1cc(Cl)c(Oc2ccc(Cl)c3ccccc23)c(Cl)c1
Reaction time: 1.5 h
Yield: 96.1 %

Procedure:
Into a 500 milliliter Parr bottle was charged 4-(4-chloro-1-naphthoxy)-3,5-dichloronitrobenzene (15.84 grams, 42.97 mmol) prepared in Part A and toluene (250 milliliters). The bottle was purged thoroughly with nitrogen and 5% platinum on carbon (0.50 grams) was added immediately following the purge. The reaction mixture was then hydrogenated for 1.5 hours on a rocking Parr hydrogenator at a pressure of 90-100 psi hydrogen at ambient temperature. The reaction mixture was filtered through a pad of celite and the filtrate concentrated under reduced pressure to afford pure 4-(4-chloro-1-naphthoxy)-3,5-dichloroaniline (13.99 grams, 41.31 mmol, 96%) as a white solid having a melting point of 145° C.-147° C. Elemental analysis of the white solid indicated the following:
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([NH2:18])=[CH:4][CH:3]=1.[NH2:19][C:20]1[C:33]2[C:32](=[O:34])[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25](=[O:35])[C:24]=2[CH:23]=[CH:22][CH:21]=1.OS(O)(=O)=O.[K]>O>[CH:10]1[CH:9]=[C:8]2[C:7]([C:6]3[C:15]([C:14](=[O:16])[C:13]2=[CH:12][CH:11]=1)=[C:2]([NH:1][C:23]1[CH:22]=[CH:21][C:20]([NH2:19])=[C:33]2[C:32]([C:31]4[C:26]([C:25](=[O:35])[C:24]=12)=[CH:27][CH:28]=[CH:29][CH:30]=4)=[O:34])[CH:3]=[CH:4][C:5]=3[NH2:18])=[O:17]
Reactant: Nc1ccc(N)c2c1C(=O)c1ccccc1C2=O
Reactant: Nc1cccc2c1C(=O)c1ccccc1C2=O
Agent: O=S(=O)(O)O
Agent: [K]
Solvent: O
Product: Nc1ccc(Nc2ccc(N)c3c2C(=O)c2ccccc2C3=O)c2c1C(=O)c1ccccc1C2=O
Reaction time: 0.5 h
Yield: 99.8 %

Procedure:
A solution of 52.0 g of 1,4-diaminoanthraquinone (92% pure) and 47.0 g of 1-aminoanthraquinone (98% pure) in 410 g of 96% strength H2SO4 is added dropwise to 410 g of water. 95.0 g of potassium peroxodisulphate is introduced into the red-orange paste at 40°-50° C. within 1 hour, the mixture is stirred for approximately a further 30 minutes and the solid is filtered off with suction. The filter cake is washed to neutrality and then stirred briefly in a mixture of 100 ml of 40% strength NaHSO3 solution and 400 ml of water. The solid is then filtered off with suction, washed with water and dried at 100° C. 96.5 g of 4,4'-diamino-1,1'-dianthrimide (84% pure), corresponding to 88% of theory, are isolated.
Reaction SMILES: [N:1]1([CH2:7][C:8]2[O:12][C:11]([CH2:13][NH:14][CH2:15][CH2:16][N:17]3[CH2:21][CH2:20][NH:19][C:18]3=[C:22]([C:25]#[N:26])[C:23]#[N:24])=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:27](OC(=O)C)(=[O:29])[CH3:28].CO>N1C=CC=CC=1>[C:27]([N:14]([CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][NH:19][C:18]1=[C:22]([C:23]#[N:24])[C:25]#[N:26])[CH2:13][C:11]1[O:12][C:8]([CH2:7][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[CH:9][CH:10]=1)(=[O:29])[CH3:28]
Reactant: N#CC(C#N)=C1NCCN1CCNCc1ccc(CN2CCCCC2)o1
Reactant: CC(=O)OC(C)=O
Solvent: CO
Solvent: c1ccncc1
Product: CC(=O)N(CCN1CCNC1=C(C#N)C#N)Cc1ccc(CN2CCCCC2)o1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 98.5 %

Procedure:
In 12 ml of pyridine was dissolved 0.6 g (1.69 mmol) of Compound 28, and 260 mg (2.55 mmol) of acetic anhydride was added dropwise. The reaction mixture was stirred at room temperature for 0.5 hour and, after addition of 1 ml of methanol, the solvent was distilled off. The residue was diluted with 20 ml of water, adjusted to pH 13 with 5N sodium hydroxide solution and extracted with methylene chloride. The extract was washed with saturated aqueous sodium chloride solution twice and dried over anhydrous magnesium sulfate. Finally the solvent was distilled off to give 0.66 g (97.9%) of Compound 44 as colorless oil.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([NH:11]C(=O)C(F)(F)F)[N:10]=2)[CH:7]=1.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][N:21]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[CH3:18][O:19][C:20]1[N:21]=[CH:22][C:23]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([CH:8]=[C:9]([NH2:11])[N:10]=3)[CH:7]=2)=[CH:24][CH:25]=1
Reactant: COc1ccc(B(O)O)cn1
Reactant: O=C(Nc1cn2cc(Br)ccc2n1)C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(-c2ccc3nc(N)cn3c2)cn1
Reaction time: 8 h

Procedure:
N-(6-Bromo-imidazo[1,2-a]pyridin-2-yl)-2,2,2-trifluoro-acetamide (Intermediate A1, step 3) (0.84 g, 2.72 mmol), 2-methoxy-5-pyridineboronic acid (0.50 g, 3.27 mmol) and dry 1,4-dioxane (10 ml) are placed in a microwave vial and purged with Argon. Pd(PPh3)4 (0.16 g, 0.14 mmol) is added followed by a solution of Cs2CO3 in water (2.66 g, 8.16 mmol in 3 ml). The reaction mixture is heated using microwave radiation at 150° C. for 45 minutes and then left overnight at room temperature. The mixture is filtered through Celite® (filter agent) and washed through with EtOAc (100 ml). The organic filtrate is washed with NaHCO3 (50 ml) and brine (50 ml), dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography on silica eluting with MeOH in DCM (1% increasing to 10%) affords the title compound. [MH+241.07].
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[CH:10]=[CH:9][S:8][C:7]=12.O.[SH2:12].[Na].Cl>CN(C)C=O>[S:8]1[C:7]2[C:2](=[S:12])[NH:3][CH:4]=[CH:5][C:6]=2[CH:10]=[CH:9]1
Reactant: Clc1nccc2ccsc12
Reactant: S
Agent: Cl
Agent: [Na]
Solvent: O
Solvent: CN(C)C=O
Product: S=c1[nH]ccc2ccsc12
Temperature: 0 °C

Procedure:
(adc) 4.85 g of 7-chloro-thieno[2,3-c]pyridine were dissolved in 15 ml of dimethylformamide and 3.18 g of sodium hydrogen sulfide monohydrate were added under argon. The mixture was heated to 110°-115° for one hour, an additional 1.06 g of sodium hydrogen sulfide monohydrate were added and the mixture was held at the temperature indicated above for an additional hour. The mixture was poured on to 150 ml of ice-water and acidified with 1N aqueous hydrochloric acid solution. After stirring at 2° for a short time, the yellowish crystals were removed by filtration. After recrystallization from a toluene/ethyl acetate mixture, there was obtained pure thieno[2,3-c]pyridine-7(6H)-thione, m.p. 187°-189°.