Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[CH2:3][C:4](Cl)=[O:5].[CH3:9][O:10][C:11]1[C:19]2[N:18]=[C:17]([CH2:20][CH2:21][CH2:22][N:23]([CH3:42])[CH2:24][CH2:25][C:26]3([OH:41])[CH2:32][CH:31]4[C:33]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)=[CH:34][CH:27]3[CH2:28][CH2:29][CH2:30]4)[NH:16][C:15]=2[CH:14]=[CH:13][CH:12]=1>>[CH3:9][O:10][C:11]1[C:19]2[N:18]=[C:17]([CH2:20][CH2:21][CH2:22][N:23]([CH3:42])[CH2:24][CH2:25][C@:26]3([O:41][C:4](=[O:5])[CH2:3][C:2]([F:8])([F:7])[F:1])[CH2:32][C@@H:31]4[C:33]([C:35]5[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=5)=[CH:34][C@H:27]3[CH2:28][CH2:29][CH2:30]4)[NH:16][C:15]=2[CH:14]=[CH:13][CH:12]=1
Reactant: O=C(Cl)CC(F)(F)F
Reactant: COc1cccc2[nH]c(CCCN(C)CCC3(O)CC4CCCC3C=C4c3ccccc3)nc12
Product: COc1cccc2[nH]c(CCCN(C)CC[C@]3(OC(=O)CC(F)(F)F)C[C@H]4CCC[C@@H]3C=C4c3ccccc3)nc12

Procedure:
Prepared according to procedure P1.4 in Example 1A using 3,3,3-trifluoropropionyl chloride and rac-(1R*,5R*,6R*)-6-(2-{[3-(4-methoxy-1H-benzoimidazol-2-yl)-propyl]-methyl-amino}-ethyl)-8-phenyl-bicyclo[3.2.2]non-8-en-6-ol.
Reaction SMILES: [C:1]12[C:7](=[N:8][CH:9]=[CH:10][CH:11]=1)[NH:6][C:5](=[O:12])[O:4][C:2]2=O.[NH:13]([CH2:15]C(O)=O)[CH3:14]>CS(C)=O>[CH3:14][N:13]1[C:2](=[O:4])[C:1]2[CH:11]=[CH:10][CH:9]=[N:8][C:7]=2[NH:6][C:5](=[O:12])[CH2:15]1
Reactant: O=c1[nH]c2ncccc2c(=O)o1
Reactant: CNCC(=O)O
Solvent: CS(C)=O
Product: CN1CC(=O)Nc2ncccc2C1=O

Procedure:
12.0 g (73.1 mmol) of 3-azaisatoic acid anhydride and 6.6 g (73.2 mmol) of sarcosine are stirred at 100° for 2.5 hours in 180 ml of dimethyl sulphoxide. The solvent is removed in a high vacuum and the oily residue is heated to 130° for about 4 hours. After cooling, the crystalline product is suspended in 150 ml of methanol. It is filtered off under suction, washed with methanol and dried. There is obtained 3,4-dihydro-4-methyl-2H-pyrido[2,3-e][1,4]diazepine-2,5(1H)-dione of melting point 245°-247°.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]([C:9](=[CH2:15])[CH2:10][C:11]([O:13][CH3:14])=[O:12])=[O:8])[CH:2]=1.[SH:16][CH2:17][CH2:18][NH:19][C:20](=[O:22])[CH3:21]>>[C:20]([NH:19][CH2:18][CH2:17][S:16][CH2:15][CH:9]([C:7](=[O:8])[C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)[CH2:10][C:11]([O:13][CH3:14])=[O:12])(=[O:22])[CH3:21]
Reactant: CC(=O)NCCS
Reactant: C=C(CC(=O)OC)C(=O)c1cccnc1
Product: COC(=O)CC(CSCCNC(C)=O)C(=O)c1cccnc1

Procedure:
The title compound was prepared from methyl 3-(3-pyridylcarbonyl)but-3-enoate and N-(2-sulfanylethyl)acetamide as described in Example 13 in quantitative yield, ESMS, (M+1)+325.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([C:12]1[O:13][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:15][N:16]=1)[CH2:9][C:10]#[CH:11]>>[C:17]1([C:14]2[O:13][C:12]([CH2:8][CH2:9][C:10]#[C:11][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=3)=[N:16][CH:15]=2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: C#CCCc1ncc(-c2ccccc2)o1
Reactant: Brc1ccccn1
Product: C(#Cc1ccccn1)CCc1ncc(-c2ccccc2)o1
Yield: 9.4 %

Procedure:
The title compound was prepared in accordance with the general method of Example 1, from 2-bromopyridine (25 mg, 0.16 mmol) and 2-(but-3-ynyl)-5-phenyloxazole (31 mg, 0.16 mmol). The crude residue was purified by flash chromatography (DCM/MeOH 99:1) and SCX column (DCM/MeOH 95:5, DCM/MeOH/NH4OH 90:5:0.1 to 90:9:1) to yield 4.0 mg (15 μmol, 9%) of 2-(4-(5-phenyloxazol-2-yl)but-1-ynyl)pyridine as a yellow oil.
Reaction SMILES: CO[C:3]([C:5]1[C:14]2[C:9](=[C:10]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH:11]=[CH:12][CH:13]=2)[N:8]=[CH:7][CH:6]=1)=[O:4].[NH3:25]>CO>[C:19]1([S:16]([NH:15][C:10]2[CH:11]=[CH:12][CH:13]=[C:14]3[C:9]=2[N:8]=[CH:7][CH:6]=[C:5]3[C:3]([NH2:25])=[O:4])(=[O:17])=[O:18])[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: N
Reactant: COC(=O)c1ccnc2c(NS(=O)(=O)c3ccccc3)cccc12
Solvent: CO
Product: NC(=O)c1ccnc2c(NS(=O)(=O)c3ccccc3)cccc12
Yield: 50 %

Procedure:
In a similar fashion using route 53 general procedure 122, 8-benzenesulfonylamino-quinoline-4-carboxylic acid methyl ester 225 (25 mg, 0.073 mmol) and NH3 in MeOH (7M; 3 ml) gave the title compound (13 mg, 50%) after purification by recrystallisation from DCM.
Reaction SMILES: [C:1]([O:5][C:6](=[O:13])[NH:7][C:8]1[S:9][CH:10]=[CH:11][N:12]=1)([CH3:4])([CH3:3])[CH3:2].[O:14]1[C:18]2([CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[O:17][CH2:16][CH2:15]1>>[C:1]([O:5][C:6](=[O:13])[NH:7][C:8]1[S:9][C:10]([C:21]2([OH:24])[CH2:22][CH2:23][C:18]3([O:17][CH2:16][CH2:15][O:14]3)[CH2:19][CH2:20]2)=[CH:11][N:12]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1nccs1
Reactant: O=C1CCC2(CC1)OCCO2
Product: CC(C)(C)OC(=O)Nc1ncc(C2(O)CCC3(CC2)OCCO3)s1

Procedure:
The title compound was prepared as a white solid from thiazol-2-yl-carbamic acid tert-butyl ester (prepared according to Das, B. et al. Tetrahedron Lett. 2006, 47, 7551-7556) and 1,4-dioxa-spiro[4.5]decan-8-one using the procedure described in Step A of Example 33.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:18][CH2:19][O:20][CH2:21][CH2:22][N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1.C1C=C(Cl)C=C(C(OO)=[O:40])C=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:18][CH2:19][O:20][CH2:21][CH2:22][N:23]([CH3:31])[C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N+:10]([O-:40])=[CH:9][C:8]=2[N:17]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COCCc1nc2cnc3ccccc3c2n1CCOCCN(C)C(=O)OC(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COCCc1nc2c[n+]([O-])c3ccccc3c2n1CCOCCN(C)C(=O)OC(C)(C)C
Reaction time: 6 h
Yield: 94.4 %

Procedure:
A solution of tert-butyl 2-{2-[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethyl(methyl)carbamate (7.20 g, 16.8 mmol) in 200 mL of CH2Cl2 was treated with MCPBA (77%, 4.32 g, 19.3 mmol). After stirring 6 h, the reaction mixture was treated with saturated NaHCO3 solution and the layers were separated. The organic portion was washed with H2O and brine then dried over Na2SO4 and concentrated to give 7.05 g of tert-butyl 2-{2-[2-(2-methoxyethyl)-5-oxido-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethyl(methyl)carbamate as a light brown solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH2:19][CH:20]=[CH:21][CH2:22]Br)=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:24]([NH:27][CH3:28])[CH:25]=[CH2:26]>>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH2:19][CH:20]=[CH:21][CH2:22][N:27]([CH2:24][CH:25]=[CH2:26])[CH3:28])=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=CCNC
Reactant: CC(C)(C)OC(=O)N1CCCc2cc(OCC=CCBr)ccc21
Product: C=CCN(C)CC=CCOc1ccc2c(c1)CCCN2C(=O)OC(C)(C)C

Procedure:
In analogy to example 2.6, 6-(4-Bromo-but-2-enyloxy)-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester and N-allyl-methylamine were converted to yield 6-[4-(Allyl-methyl-amino)-but-2-enyloxy]-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butyl ester as colorless oil, MS: 373 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]([O:14][CH3:15])=[O:13])=[CH:6][C:5]2=[O:16].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C.I[CH2:29][CH3:30]>O>[CH2:29]([O:16][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=2)[N:8]=[C:7]([C:12]([O:14][CH3:15])=[O:13])[CH:6]=1)[CH3:30]
Reactant: COC(=O)c1cc(=O)c2cc(F)ccc2[nH]1
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOc1cc(C(=O)OC)nc2ccc(F)cc12
Temperature: 50 °C
Reaction time: 1 h

Procedure:
8.0 g (0.036 M) of methyl 6-fluoro-4-oxo-1,4-dihydroquinoline-2-carboxylate and 15.0 g (0.108 M) of potassium carbonate are introduced into 80 ml of DMF. The reaction mixture is stirred for 1 hour at 50° C. After addition of 3.0 ml (0.037 M) of iodoethane and heating for 12 hours at 50° C., the reaction medium is poured into 400 ml of demineralized water. A brown solid precipitates out. The solid is filtered off, washed thoroughly with water and then with isopropyl ether, and finally dried under vacuum at 40° C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([SH:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].[OH-].[K+].Cl.Cl[CH2:15][CH2:16][N:17]([CH2:20][CH3:21])[CH2:18][CH3:19].O>CN(C)C=O>[CH2:16]([N:17]([CH2:20][CH3:21])[CH2:18][CH2:19][S:10][C:7]1[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1)[CH3:15]
Reactant: O=[N+]([O-])c1ccc(S)cc1
Reactant: CCN(CC)CCCl
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: O
Product: CCN(CC)CCSc1ccc([N+](=O)[O-])cc1
Temperature: 100 °C

Procedure:
To a solution of 7.0 g (45 mmol) of 4-nitrothiophenol and 22.5 mL of 4N aqueous potassium hydroxide in 40 mL of dimethylformamide add a solution of 9.53 g (55 mmol) of 2-chloro-N,N-diethylethanamine hydrochloride in 40 mL of dimethylformamide. Heat the reaction mixture for about 3 h at 100° C. After this time, cool the mixture to room temperature and add 150 mL of water. Extract th aqueous mixture with 3×200 mL of methylene chloride. Combine the methylene chloride extracts and extract these with 200 mL of 1N aqueous hydrochloric acid. Make the acid extract basic with saturated aqueous sodium bicarbonate solution
Reaction SMILES: O.Cl.[C:3]([C:7]1[CH:8]=[C:9]([C:18]2[O:19][CH:20]=[C:21]([CH2:23][CH2:24]OC3C=CC(CNCC)=CC=3)[N:22]=2)[CH:10]=[C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:12]=1[OH:13])([CH3:6])([CH3:5])[CH3:4].C(C1C=C(C2OC=C(CCOC3C=CC(CNCC)=CC=3)N=2)C=C(C(C)(C)C)C=1O)(C)(C)C.Cl.[CH:70]([C:72]1[CH:73]=[C:74]([CH:77]=[CH:78][C:79]=1[OH:80])[CH:75]=[O:76])=[O:71].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:14]([C:11]1[CH:10]=[C:9]([C:18]2[O:19][CH:20]=[C:21]([CH2:23][CH2:24][O:80][C:79]3[CH:78]=[CH:77][C:74]([CH:75]=[O:76])=[CH:73][C:72]=3[CH:70]=[O:71])[N:22]=2)[CH:8]=[C:7]([C:3]([CH3:4])([CH3:5])[CH3:6])[C:12]=1[OH:13])([CH3:15])([CH3:16])[CH3:17]
Reactant: O=Cc1ccc(O)c(C=O)c1
Reactant: CCNCc1ccc(OCCc2coc(-c3cc(C(C)(C)C)c(O)c(C(C)(C)C)c3)n2)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)c1cc(-c2nc(CCOc3ccc(C=O)cc3C=O)co2)cc(C(C)(C)C)c1O
Yield: 48.9 %

Procedure:
In a flask, 4.75 g (15 mmole) of the compound of Example 1 C, 2.36 g (15.75 mmole) of 3-formyl-4-hydroxybenzaldehyde, and 3.93 g (15 mmole) of triphenylphosphine were dissolved in 45 ml tetrahydrofuran with stirring, under nitrogen. The solution was chilled to −10° and a solution of 2.36 ml (15 mmole) diethyl azodicarboxylate in 15 ml. Tetrahydrofuran was added over 10 minutes, with stirring. The reaction exothermed to +1° C. The bath was removed and the reaction stirred under nitrogen for 18 hours. The reaction was then stripped, dissolved in a minimum amount of methylene chloride and placed in the freezer. The diethoxycarbonylhydrazine was then filtered off and the filtrate was chromatographed, Prep 500, two columns, eluting with 0 to 20% ethyl acetate/toluene gradient over 30 minutes. The appropriate fractions were bulked and stripped to give 3.3 g (49%) product which was used without further purification.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[C@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]1[C:10]([C:12]1N=C(C)S[C:16]=1[C:17]1[CH:22]=[CH:21][C:20](F)=C[CH:18]=1)=[O:11].CC1C=CC([N:35]2[N:39]=[CH:38][CH:37]=[N:36]2)=C(C=1)C(O)=O>>[NH2:1][CH2:2][C@H:3]1[C@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]1[C:10]([C:12]1[CH:16]=[C:17]([CH3:18])[CH:22]=[CH:21][C:20]=1[N:35]1[N:39]=[CH:38][CH:37]=[N:36]1)=[O:11]
Reactant: Cc1ccc(-n2nccn2)c(C(=O)O)c1
Reactant: Cc1nc(C(=O)N2CCC[C@@H](C)[C@@H]2CN)c(-c2ccc(F)cc2)s1
Product: Cc1ccc(-n2nccn2)c(C(=O)N2CCC[C@@H](C)[C@@H]2CN)c1

Procedure:
The title compound was prepared following the same general protocol as described for rac-trans-(2-(aminomethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone in Example A65 using 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid. MS (ESI) 314 (M+H).
Reaction SMILES: [C:1]([Si:5]([CH3:19])([CH3:18])[O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH:9](OS(C)(=O)=O)[CH2:8]1)([CH3:4])([CH3:3])[CH3:2].[Si](OC1CCC([N:33]2[CH2:37][C:36]([B:38]3[O:42][C:41]([CH3:44])([CH3:43])[C:40]([CH3:46])([CH3:45])[O:39]3)=[CH:35][NH:34]2)C1)(C(C)(C)C)(C)C>>[C:1]([Si:5]([CH3:19])([CH3:18])[O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH:9]([N:33]2[CH2:37][C:36]([B:38]3[O:39][C:40]([CH3:46])([CH3:45])[C:41]([CH3:44])([CH3:43])[O:42]3)=[CH:35][NH:34]2)[CH2:8]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OC1CCCC(OS(C)(=O)=O)C1
Reactant: CC1(C)OB(C2=CNN(C3CCC(O[Si](C)(C)C(C)(C)C)C3)C2)OC1(C)C
Product: CC1(C)OB(C2=CNN(C3CCCC(O[Si](C)(C)C(C)(C)C)C3)C2)OC1(C)C
Yield: 10 %

Procedure:
The title compound was prepared in 10% yield from methanesulfonic acid 3-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl ester by a procedure analogous to Intermediate 28, Step C. The crude compound was purified by column chromatography (25% ethyl acetate:hexanes and then DCM) to afford the title compound. 1H NMR (300 MHz, CDCl3): δ 7.76 (s, 1H), 7.27 (s, 1H), 4.45-4.63 (m, 1H), 4.23 (br. s, 1H), 2.05-2.09 (m, 2H), 1.5-1.9 (m, 6H), 1.45 (s, 9H), 1.31 (s, 12H), 0.05 (s, 6H).
Reaction SMILES: [F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([C:13]([CH3:49])([CH3:48])[C:14]([N:16]([CH3:47])[C:17]2[C:18]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:40]=3[CH3:46])=[CH:19][C:20]([C:23]#[C:24][CH2:25][C@@H:26]([NH:31]C(OC(C)(C)C)=O)[C:27]([O:29][CH3:30])=[O:28])=[N:21][CH:22]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(O)(C(F)(F)F)=O>ClCCl>[NH2:31][C@H:26]([CH2:25][C:24]#[C:23][C:20]1[CH:19]=[C:18]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:40]=2[CH3:46])[C:17]([N:16]([C:14](=[O:15])[C:13]([C:5]2[CH:4]=[C:3]([C:2]([F:50])([F:51])[F:1])[CH:8]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:6]=2)([CH3:48])[CH3:49])[CH3:47])=[CH:22][N:21]=1)[C:27]([O:29][CH3:30])=[O:28]
Reactant: COC(=O)[C@@H](CC#Cc1cc(-c2ccc(F)cc2C)c(N(C)C(=O)C(C)(C)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cn1)NC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)[C@H](N)CC#Cc1cc(-c2ccc(F)cc2C)c(N(C)C(=O)C(C)(C)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of methyl (2R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentynoate (Intermediate 12, 1 g, 1.382 mmol) in Dichloromethane (15 ml), TFA (5 ml, 64.9 mmol) was added and the reaction mixture was stirred for 1 h at r.t. The solvent and the excess of TFA were evaporated and the residue purified by SPE-SCX cartridge to obtain Intermediate 13. This residue was dissolved in Acetonitrile (14 ml) and Silver trifluoromethanesulfonate (0.036 g, 0.138 mmol) was added; the reaction mixture was stirred for 6 hours at 60° C. The solvent was evaporated and the residue was dissolved in DCM (15 ml) and the metal catalyst was filtered off.
Reaction SMILES: N1C=CC=CC=1.[F:7][C:8]([F:21])([F:20])[S:9]([O:12]S(C(F)(F)F)(=O)=O)(=[O:11])=[O:10].O[C:23]1[CH:24]=[C:25]([C:35]([O:37][CH3:38])=[O:36])[CH:26]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:28]=1.[Cl-].[NH4+]>C(Cl)(Cl)Cl>[F:7][C:8]([F:21])([F:20])[S:9]([O:12][C:23]1[CH:24]=[C:25]([C:35]([O:37][CH3:38])=[O:36])[CH:26]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:28]=1)(=[O:11])=[O:10]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: COC(=O)c1cc(O)cc(-c2ccccc2)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: COC(=O)c1cc(OS(=O)(=O)C(F)(F)F)cc(-c2ccccc2)c1
Reaction time: 0.5 h

Procedure:
With cooling with ice, pyridine (1.2 mL) and trifluoromethanesulfonic acid anhydride (1.2 mL) were added to a CHCl3 (40 mL) solution of methyl 5-hydroxybiphenyl-3-carboxylate, and stirred for 30 minutes with cooling with ice. Aqueous ammonium chloride was added to the reaction liquid, extracted with ethyl acetate, and the organic layer was washed with water, aqueous saturated sodium bicarbonate solution and saturated saline water. This was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the title compound as a yellow oil. Not purified, this was used in the next step.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][O:11][C:12]1[CH:13]=[C:14]([N+:18]([O-])=[O:19])[CH:15]=[CH:16][CH:17]=1.O.NN>O1CCCC1.[Pd]>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][O:11][C:12]1[CH:13]=[C:14]([NH:18][OH:19])[CH:15]=[CH:16][CH:17]=1
Reactant: O=[N+]([O-])c1cccc(OCc2nc3ccccc3s2)c1
Agent: [Pd]
Agent: NN
Solvent: C1CCOC1
Solvent: O
Product: ONc1cccc(OCc2nc3ccccc3s2)c1
Yield: 85.4 %

Procedure:
To a solution of 3-[(2-benzthiazolyl)methoxy]nitrobenzene (1.6 g), prepared as in Example 1B, in tetrahydrofuran with 10% palladium on carbon is slowly added hydrazine hydrate (0.4 ml). Fresh catalyst is added twice over 4 hours. The mixture is filtered through celite and the solvent is removed in vacuo to give 1.3 g (81% yield) of product, m.p. 112°-114° C.
Reaction SMILES: [Cl:1][C:2]1[N:3]([CH2:10][C@@:11]([OH:19])([CH3:18])[CH2:12]OS(C)(=O)=O)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1.C1CCN2C(=NCCC2)CC1>C(Cl)Cl>[Cl:1][C:2]1[N:3]([CH2:10][C@@:11]2([CH3:18])[CH2:12][O:19]2)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1
Reactant: C[C@@](O)(COS(C)(=O)=O)Cn1cc([N+](=O)[O-])nc1Cl
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: C[C@]1(Cn2cc([N+](=O)[O-])nc2Cl)CO1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 91.3 %

Procedure:
(S)-2-Chloro-1-(2-hydroxy-2-methyl-3-methanesulfonyloxypropyl)-4-nitroimidazole prepared in Example 17 (3.02 g, 9.51 mmol) was dissolved in methylene chloride (30 ml). DBU (1.7 ml, 11.41 mmol) was added to the solution, and the resulting mixture was stirred at room temperature for 1.5 hours. The reaction mixture was washed with 3N hydrochloric acid (30 ml) and saturated saline solution (20 ml) in this order, dried over magnesium sulfate and then filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate=20/1) to afford (S)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole (1.89 g, yield 91%) as a light yellow solid.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[NH2:4].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:17][C:18]1[N:23]=[CH:22][CH:21]=[CH:20][N:19]=1>CN(C)C=O.[I-].[K+]>[N:19]1[CH:20]=[CH:21][CH:22]=[N:23][C:18]=1[CH2:17][NH:4][C:3]1[C:5]([CH3:9])=[CH:6][CH:7]=[CH:8][C:2]=1[CH3:1]
Reactant: Cc1cccc(C)c1N
Reactant: ClCc1ncccn1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cccc(C)c1NCc1ncccn1
Temperature: 100 °C
Reaction time: 5 h
Yield: 70.3 %

Procedure:
48.4 g (0.4 mol) of 2,6-dimethylaniline, 55.3 g (0.4 mol) of potassium carbonate and 0.2 g of potassium iodide were heated to 100° C. in 60 ml of dimethylformamide, and 25.7 g (0.2 mol) of 2-chloromethyl-pyrimidine were then added dropwise. The reaction mixture was subsequently stirred at 100° C. for 5 hours and then poured onto 500 g of ice. It was then extracted three times with 150 ml of methylene chloride each time. The combined organic phases were dried over sodium sulphate and concentrated in vacuo. The residue was distilled under a high vacuum. 30 g (70% of theory) of N-(pyrimidin-2-yl-methyl)-2,6-dimethylaniline were obtained as a colorless oil of boiling point 150° C./0.2 mm Hg. ##STR13##
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]([F:11])([F:10])[F:9].[N:12]1([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1>>[C:21]([O:20][C:18]([N:12]1[CH2:17][CH2:16][N:15]([C:2]2[CH:7]=[CH:6][N:5]=[CH:4][C:3]=2[C:8]([F:11])([F:10])[F:9])[CH2:14][CH2:13]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]
Reactant: FC(F)(F)c1cnccc1Cl
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Product: CC(C)(C)OC(=O)N1CCN(c2ccncc2C(F)(F)F)CC1

Procedure:
The reaction of 4-chloro-3-trifluoromethylpyridine (2.05 g, 9.4 mmol, Matrix Scientific) and tert-butyl 1-piperazinecarboxylate (2.1 g, 11.3 mmol, Aldrich) under the conditions of Example 3a afforded the crude product, which was purified by silica gel column chromatography (60% EtOAc/hexane) to give the title compound as a white solid. MS (ESI, pos. ion) m/z: 332 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[C:9](\Cl)/[C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][CH2:18][CH3:19])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[OH-].[K+]>O1CCOCC1.CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][C:10]2[CH:11]=[CH:12][C:13]([CH2:16][CH2:17][CH2:18][CH3:19])=[CH:14][CH:15]=2)=[CH:6][CH:7]=1
Reactant: CCCCc1ccc(/C(Cl)=C/c2ccc(Br)cc2)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1COCCO1
Product: CCCCc1ccc(C#Cc2ccc(Br)cc2)cc1
Yield: 89.6 %

Procedure:
To a 1 L flask containing a solution of 1-bromo-4-[(Z) -2-chloro-2-(4-butyl-phenyl) vinyl] benzene (VIe) (100 g; 0.285 mol) in 1,4-dioxane (500 mL; 5 vols) and MeOH (200 mL; 2vols), KOH (32 g; 0.571 mol) was added in one portion. Protocol and work-up was then similar with those described above. Title compound (m=80 g) was obtained in a 89% yield. Melting point: 75.6-76.1° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:18])[CH:9]=[CH:10][C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[CH:5]=[CH:6][CH:7]=1.[NH4+].[Cl-]>CO.O.[Zn]>[Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:18])[CH2:9][CH2:10][C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(C=Cc1ccc(Cl)cc1)c1cccc(Cl)c1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: O
Product: O=C(CCc1ccc(Cl)cc1)c1cccc(Cl)c1
Temperature: 25 °C
Yield: 82.4 %

Procedure:
1-(3-chlorophenyl)-3-(4-chlorophenyl)prop-2-en-1-one (1.38 g, 5 mmol), Zn dust (1.95 g, 30 mmol), NH4Cl (2.67 g, 50 mmol) were combined in MeOH (10 mL) and water (5 mL). The reaction was refluxed for 4 h, cooled to RT then filtered. The filtrate was concentrated to a residue which was purified by chromatography PE/EA (5:1) to give 1-(3-chlorophenyl)-3-(4-chlorophenyl)propan-1-one (1.15 g, 83% yield) as a brown solid. MH+ 279 and TR=2.025 min.
Reaction SMILES: [CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6](=[O:13])[N:5]2[CH2:14][CH2:15][CH2:16][CH:4]2[C:3]1=[O:17].[N+:18]([O-])([O-:20])=[O:19].[K+]>S(=O)(=O)(O)O>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][C:11]([N+:18]([O-:20])=[O:19])=[CH:12][C:7]=2[C:6](=[O:13])[N:5]2[CH2:14][CH2:15][CH2:16][CH:4]2[C:3]1=[O:17]
Reactant: O=[N+]([O-])[O-]
Reactant: CN1C(=O)C2CCCN2C(=O)c2ccccc21
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CN1C(=O)C2CCCN2C(=O)c2cc([N+](=O)[O-])ccc21
Reaction time: 2 h

Procedure:
To 10-methyl-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazapine-5,11(10H,11aH)-dione (5.7 g, 24.7 mmol) in concentrated sulfuric acid (60 ml) at 0° C. was added potassium nitrate (2.62 g, 25.9 mmol). After stirring for 2 h the mixture was dumped onto ice (500 g) and extracted with ethyl acetate (5×75 ml). The combined extracts were washed with water, dried over magnesium sulfate, filtered, and concentrated to a solid which was recrystallized from ethyl acetate-hexane (5.2 g, 77%), m.p. 160-162° C.