Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:20]=[CH:19][C:7]([C:8]([C:10]2[N:14]([CH3:15])[C:13]([CH2:16][C:17]#[N:18])=[CH:12][CH:11]=2)=[O:9])=[CH:6][CH:5]=1.[CH3:21]I>COCCOC>[Cl:3][C:4]1[CH:20]=[CH:19][C:7]([C:8]([C:10]2[N:14]([CH3:15])[C:13]([CH:16]([CH3:21])[C:17]#[N:18])=[CH:12][CH:11]=2)=[O:9])=[CH:6][CH:5]=1
Reactant: CI
Reactant: Cn1c(CC#N)ccc1C(=O)c1ccc(Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: CC(C#N)c1ccc(C(=O)c2ccc(Cl)cc2)n1C
Reaction time: 1 h

Procedure:
To a suspension of sodium hydride (12.2 g. of 50% w/w NaH in mineral oil) in 1,2-dimethoxyethane is added 5-(p-chlorobenzoyl)-1-methylpyrrole-2-acetonitrile (62.6 g., 0.24 mole) in 1,2-dimethoxyethane over a period of 1/2 hr. at room temperature. After the addition is complete, the mixture is stirred for 1 hour and then 35 g. (0.25 mole) of methyl iodide is added. The reaction mixture is stirred for an additional 3 hours, concentrated under reduced pressure, diluted with water and extracted with chloroform. After drying, the chloroform is removed leaving a brown solid residue which is triturated with cold methanol to give yellow crystals of 5-(p-chlorobenzoyl)-α-methyl-1-methylpyrrole-2-acetonitrile, m.p. 145-148° C. Two recrystallizations from methanol raises the m.p. to 151.5-152.5° C.
Reaction SMILES: B(Br)(Br)Br.C[O:6][C:7]1[CH:8]=[C:9]([CH:15]=[CH:16][C:17]2[O:21][N:20]=[C:19]([CH2:22][CH:23]3[CH2:28][CH2:27][N:26]([CH:29]([CH3:31])[CH3:30])[CH2:25][CH2:24]3)[N:18]=2)[CH:10]=[CH:11][C:12]=1[O:13]C>ClCCl.N>[CH:29]([N:26]1[CH2:27][CH2:28][CH:23]([CH2:22][C:19]2[N:18]=[C:17]([CH:16]=[CH:15][C:9]3[CH:8]=[C:7]([OH:6])[C:12]([OH:13])=[CH:11][CH:10]=3)[O:21][N:20]=2)[CH2:24][CH2:25]1)([CH3:31])[CH3:30]
Reactant: COc1ccc(C=Cc2nc(CC3CCN(C(C)C)CC3)no2)cc1OC
Agent: BrB(Br)Br
Agent: N
Solvent: ClCCl
Product: CC(C)N1CCC(Cc2noc(C=Cc3ccc(O)c(O)c3)n2)CC1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
Boron tribromide (0.229 mL, 2.42 mmol) was added dropwise to a cooled solution of 4-{5-[2-(3,4-Dimethoxy-phenyl)-vinyl]-[1,2,4]oxadiazol-3-ylmethyl}-1-isopropyl-piperidine (compound of Example 21; 0.15 g, 0.4 mmol) in dichloromethane (5 mL) at −78° C. The reaction mixture was warmed to room temperature and stirred for 6 h. The reaction mixture was quenched with methanol (2 mL) and the organic solvent was evaporated. The residue obtained was dissolved in 8% methanolic ammonia (5 mL) and the inorganic solid obtained was removed by filtration. The filtrate was concentrated and purified by column chromatography (silica gel, 3% methanol in chloroform) to afford the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8]C)[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:27])[C:11]([C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=[N:19][CH:18]=1)([OH:16])[C:12]([F:15])([F:14])[F:13].Br>>[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:27])[C:11]([C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=[N:19][CH:18]=1)([OH:16])[C:12]([F:15])([F:13])[F:14]
Reactant: COc1ccc(C(C)C(O)(c2cnnc3ccccc23)C(F)(F)F)c(Cl)c1
Agent: Br
Product: CC(c1ccc(O)cc1Cl)C(O)(c1cnnc2ccccc12)C(F)(F)F

Procedure:
The title compound was prepared in analogy to Example 72 from 3-(2-chloro-4-methoxy-phenyl)-2-cinnolin-4-yl-1,1,1-trifluoro-butan-2-ol (Example 107) by treatment with aqueous HBr. MS (m/e)=383.2 (MH+).
Reaction SMILES: [OH:1][CH:2]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:9])[CH3:8].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.CCOCC>ClCCl>[O:1]=[C:2]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:9])[CH3:8]
Reactant: CCCCCCC/C=C\CCCCCCCC(O)CCCNC(C)=O
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: CCCCCCC/C=C\CCCCCCCC(=O)CCCNC(C)=O

Procedure:
A 0.5 g portion of N-(4-hydroxy-12(Z)-eicosenyl)acetamide was stirred with 0.44 g of pyridinium chlorochromate in 15 ml of dichloromethane for 2 hours. This mixture was poured into 50 ml of ether and filtered through hydrous magnesium silicate. The filtrate was evaporated giving 0.24 g of the desired product as a pale yellow solid, mp 51°-52° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36](Br)[CH:35]=1)[C:9]1[CH:10]=[C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[C:33]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[C:27]4[C:22]3=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH:16]=2)[CH:12]=[CH:13][CH:14]=1.C(=O)=O.C([Li])CCC.Cl[Si:50](Cl)([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>CC(C)=O.C1COCC1>[CH:23]1[C:22]2[N:21]([C:17]3[CH:16]=[C:15]([C:11]4[CH:12]=[CH:13][CH:14]=[C:9]([N:8]5[C:3]6[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=6[Si:50]([C:57]6[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=6)([C:51]6[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=6)[C:35]6[CH:36]=[CH:37][CH:38]=[CH:39][C:34]5=6)[CH:10]=4)[CH:20]=[CH:19][CH:18]=3)[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]=2[CH:26]=[CH:25][CH:24]=1
Reactant: Brc1cccc(N(c2cccc(-c3cccc(-n4c5ccccc5c5ccccc54)c3)c2)c2ccccc2Br)c1
Reactant: Cl[Si](Cl)(c1ccccc1)c1ccccc1
Agent: O=C=O
Agent: [Li]CCCC
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: c1ccc([Si]2(c3ccccc3)c3ccccc3N(c3cccc(-c4cccc(-n5c6ccccc6c6ccccc65)c4)c3)c3ccccc32)cc1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
N-(2-bromophenyl)-N-(3-bromophenyl)-3′-(9H-carbazol-9-yl)-[1,1′-biphenyl]-3-amine was added into a 250 mL round bottom flask, and solubilized in dry THF (155 ml). The solution was cooled down to −78° C. using dry ice and Acetone. Butyllithium (7.45 ml, 18.62 mmol) was added dropwise and the reaction mixture was stirred −78° C. for 2 hours. Dichlorodiphenylsilane (2.108 ml, 10.24 mmol) was then added dropwise. The reaction mixture was allowed to slowly warm to room temperature and was stirred overnight. The reaction was quenched with water, extracted three times with ether, washed with brine and water. The crude material was purified with column chromatography using hexane/DCM (75/25). The product was collected as a white powder with a purity of 99.3% by HPLC. The product was recrystallized twice from DCM and hexane. The target 5-(3′-(9H-carbazol-9-yl)-[1,1′-biphenyl]-3-yl)-10,10-diphenyl-5,10-dihydrodibenzo[b,e][1,4]azasiline (Compound 10) was afforded as a white powder (1.8 g, 29% yield). Compound 10 was then sublimed and 1.2 g was collected.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH2:15][O:14][C:13](=[O:16])[C:12]=2[C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=O)=[CH:28][CH:27]=1>N1CCCCC1.C(O)C>[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=[C:15]2[O:14][C:13](=[O:16])[C:12]([C:17]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[O:18])=[C:11]2[C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)=[CH:28][CH:27]=1
Reactant: COc1ccc(C2=C(C(=O)N3CCOCC3)C(=O)OC2)cc1OC
Reactant: O=Cc1ccc(Cl)cc1
Solvent: C1CCNCC1
Solvent: CCO
Product: COc1ccc(C2=C(C(=O)N3CCOCC3)C(=O)OC2=Cc2ccc(Cl)cc2)cc1OC

Procedure:
4-(3,4-Dimethoxyphenyl)-2-oxo-2,5-dihydrofurane-3-carboxylic acid morpholide (1.00 g, 3 mmol) and 4-chlorobenzaldehyde (0.42 g, 3 mmol) were refluxed with ethanol (15 ml) and a small amount of piperidine (3 drops) for 3 h, then the reaction mixture was concentrated. The residue was dissolved in ethyl acetate (5 ml), petrol ether (2.5 ml) was added and the solution was applied onto a flash chromatography column (silica gel, 30 g). The column was eluted with ethyl acetate/petrol ether (2:1). The fractions containing the compound with the Rf (ethyl acetate/petrol ether, 2:1): 0.32 were collected and concentrated. 5-(4-Chlorobenzylidene)-4-(3,4-dimethoxyphenyl)-2-oxo-2,5-dihydro-furane-3-carboxylic acid morpholide was precipitated by addition of petrol ether.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[Br:9]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl.C(=O)(O)[O-].[Na+]>[Br:1][C:2]1[C:3]([CH2:8][Br:9])=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ncccc1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Product: BrCc1ncccc1Br
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a room temperature solution of 3-bromo-2-methylpyridine (2.60 g, 15.1 mmol) and N-bromosuccinimide (NBS) (2.90 g, 16.3 mmol) in CCl4 is added benzoyl peroxide (150 mg, 1.08 mmol). The mixture is heated at reflux for 7 hours, cooled to room temperature, diluted with saturated aqueous sodium bicarbonate (30 mL) and extracted with ethyl acetate (EtOAc) (3×30 mL). The combined organic layers are washed with brine (3×30 mL), dried over magnesium sulfate, filtered and concentrated. LCMS analysis indicated starting material and the desired product. The residue is dissolved in CCl4 (40 mL) and NBS (1.7 g, 9.6 mmol) and benzoyl peroxide (100 mg, 0.72 mmol) is added, and the mixture is warmed at reflux. After 24 hours, the mixture is cooled to room temperature, diluted with saturated aqueous sodium bicarbonate (30 mL) and extracted with EtOAc (3×30 mL). The combined organic layers are washed with brine (3×30 mL), dried over magnesium sulfate, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a mixture of dichloromethane in hexanes (25:75, then 3:7) to afford 3-bromo-2-bromomethyl-pyridine.
Reaction SMILES: [C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([CH2:14][C:15]3[NH:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[N:16]=3)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C)C=O.[H-].[Na+].Cl[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=1>O>[F:39][C:36]1[CH:37]=[CH:38][C:33]([CH2:32][N:19]2[C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=[C:15]2[CH2:14][CH:11]2[CH2:10][CH2:9][N:8]([CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:13][CH2:12]2)=[CH:34][CH:35]=1
Reactant: c1ccc(CN2CCC(Cc3nc4ccccc4[nH]3)CC2)cc1
Reactant: Fc1ccc(CCl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Fc1ccc(Cn2c(CC3CCN(Cc4ccccc4)CC3)nc3ccccc32)cc1
Reaction time: 1 h
Yield: 90 %

Procedure:
To a stirred mixture of 55 parts of 2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-benzimidazole and 450 parts of N,N-dimethylformamide were added 10.6 parts of a sodium hydride dispersion 50% and stirring was continued for 1 hour. Then there were added dropwise 26 parts of 1-(chloromethyl)-4-fluorobenzene (slightly exothermic reaction). Upon completion, stirring was continued overnight at room temperature. Water was added and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The solid residue was stirred in 1,1'-oxybisethane. The product was filtered off and dried, yielding 67.6 parts (90%) of 1-[(4-fluorophenyl)methyl]-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-benzimidazole; mp. 127.5° C. (34).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]([NH2:18])=[S:17])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.Br[CH:20]1[CH2:25][CH2:24][CH2:23][CH:22]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=2[Cl:33])[C:21]1=O>C(O)C>[Cl:33][C:27]1[CH:28]=[C:29]([Cl:32])[CH:30]=[CH:31][C:26]=1[CH:22]1[C:21]2[N:18]=[C:16]([NH:15][C:5]3[CH:6]=[CH:7][C:8]([N:9]4[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]4)=[C:3]([O:2][CH3:1])[CH:4]=3)[S:17][C:20]=2[CH2:25][CH2:24][CH2:23]1
Reactant: O=C1C(Br)CCCC1c1ccc(Cl)cc1Cl
Reactant: COc1cc(NC(N)=S)ccc1-n1cnc(C)c1
Solvent: CCO
Product: COc1cc(Nc2nc3c(s2)CCCC3c2ccc(Cl)cc2Cl)ccc1-n1cnc(C)c1
Temperature: 25 °C
Yield: 36.9 %

Procedure:
A suspension of [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea (62 mg, 0.24 mmol) and of crude 2-bromo-6-(2,4-dichloro-phenyl)-cyclohexanone (79 mg, 0.25 mmol) in ethanol (2 mL) was heated to reflux under an atmosphere of nitrogen for 3 days. After cooling to room temperature the solvent was evaporated under reduced pressure and the residue was purified by reversed preparative HPLC using acetonitril/water (0.1% formic acid) to yield the title compound (43 mg, 37%) as an off-white solid. MS ISP (m/e): 485.3/487.3 (100/73) [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=8.00 (s, 1H), 7.47 (s, 1H), 7.39 (s, 1H), 7.11 (m, 2H), 6.89 (m, 2H), 6.75 (d, 1H), 4.47 (m, 1H), 3.60 (s, 3H), 2.76 m, 2H), 2.38 (s, 3H), 2.22 (m, 1H), 1.86 (m, 3H).
Reaction SMILES: C([N:5]1[C:9](=O)[N:8]2[CH:11]=[CH:12][N:13]=[C:7]2[S:6]1)CCC.N#C[Br:16]>ClCCl>[Br:16][C:9]1[N:8]2[CH:11]=[CH:12][N:13]=[C:7]2[S:6][N:5]=1
Reactant: N#CBr
Reactant: CCCCn1sc2nccn2c1=O
Solvent: ClCCl
Product: Brc1nsc2nccn12
Temperature: 25 °C
Reaction time: 16 h
Yield: 90.1 %

Procedure:
To a cooled solution of 2-butylimidazo[1,2-d]-1,2,4-thiadiazole-3(2H)-one (4.78 g, 0.0242 mole) in 25 mL dichloromethane, cyanogen bromide (5.13 g, 0.0482 mole) was added in one portion and the mixture was stirred for 16 h at room temperature. The precipitate was filtered, slurried in 10 mL of methanol and subsequently washed with dichloromethane to give 4.45 g (90%) of 3-bromoimidazo[1,2-d]-1,2,4-thiadiazole as a colourless powder: mp 220° C. (dec); MS m/z 205, 203 (M+). Anal. Calcd for C4H2N3SBr · 1/2 H2O: C, 22.55; H, 1.42; N, 19.72; O, 3.75; S, 15.02; Br, 37.50. Found: C, 22.79; H, 1.41; N, 19.42; O, 2.67; S, 14.61; Br, 38.20.
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][OH:13])=[CH:8][N:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1>C(Cl)(Cl)Cl.O=[Mn]=O>[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH:12]=[O:13])=[CH:8][N:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: OCc1ccc(-n2ccnc2)nc1
Agent: O=[Mn]=O
Solvent: ClC(Cl)Cl
Product: O=Cc1ccc(-n2ccnc2)nc1

Procedure:
MnO2 (18.17 g) is added to a solution of the hydroxy methyl compound of Step 3. above (6.1 g) in CHCl3, and the resulting reaction mixture heated to reflux for 22 hours, allowed to cool, filtered, and the organic layer evaporated affording the desired product as a white solid. M.P.=136°-137.5° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[N:10]([CH3:11])[C:9](=[O:12])[O:8][C:6](=O)[C:5]2=[CH:13][CH:14]=1.[N:15]1([CH2:20][CH:21]([CH3:24])[CH2:22][NH2:23])[CH:19]=[CH:18][N:17]=[CH:16]1>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:6](=[O:8])[N:23]([CH2:22][CH:21]([CH3:24])[CH2:20][N:15]3[CH:19]=[CH:18][N:17]=[CH:16]3)[C:9](=[O:12])[N:10]2[CH3:11])=[CH:13][CH:14]=1
Reactant: Cn1c(=O)oc(=O)c2ccc(Cl)cc21
Reactant: CC(CN)Cn1ccnc1
Solvent: CCO
Product: CC(Cn1ccnc1)Cn1c(=O)c2ccc(Cl)cc2n(C)c1=O
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A mixture of 2.12 g of 4-chloro-N-methylisatoic anhydride, 1.39 g of 3-(1H-imidazol-1-yl)-2-methylpropanamine and 20 ml of ethanol was stirred at room temperature for 20 hours and concentrated. Ethyl chloroformate (10 ml) was added and the mixture was heated in an oil bath at 90°-105° C. for 2 hours, dissolved in ethanol and concentrated. Ethanol (25 ml) and 2.0 g of potassium hydroxide was added and the mixture was heated at reflux for 3 hours and concentrated. Water was added, and the pH was adjusted to 6-7 with acetic acid. The product was extracted into methylene chloride. Concentration and recrystallization from ethyl acetate resulted in the desired product, mp 206°-209° C.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[C:8]([NH2:10])[CH:9]=[C:4]2[CH:3]=[CH:2]1.[Cl:11][C:12]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:13]=1[C:14](Cl)=[O:15]>N1C=CC=CC=1.ClCCl>[Cl:11][C:12]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:13]=1[C:14]([NH:10][C:8]1[CH:9]=[C:4]2[CH:3]=[CH:2][NH:1][C:5]2=[N:6][CH:7]=1)=[O:15]
Reactant: O=C(Cl)c1cc([N+](=O)[O-])ccc1Cl
Reactant: Nc1cnc2[nH]ccc2c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(Nc1cnc2[nH]ccc2c1)c1cc([N+](=O)[O-])ccc1Cl

Procedure:
1.87 g 1H-Pyrrolo[2,3-b]pyridin-5-ylamine in 60 ml dry pyridine were treated dropwise at RT with a solution of 6.79 g 2-chloro-5-nitrobenzoyl chloride in 10 ml dichloromethane. Stirring was continued over night. The mixture was evaporated and the residue was treated with 25 ml methanol and 10 ml conc. ammonia for 2 hrs at RT. The solvents are again evaporated and the residue is dispersed in water. The crude product is isolated by filtration and washed thoroughly with water and diethylether.
Reaction SMILES: O.O.O.C([O-])(=O)C.[Pb+2].C([O-])(=O)C.[N+:13]([C:16]1[CH:23]=[CH:22][C:19]([CH2:20][SH:21])=[CH:18][CH:17]=1)([O-:15])=[O:14].Br[N:25]1[C:29](=[O:30])[CH2:28][CH2:27][C:26]1=[O:31]>CO>[N+:13]([C:16]1[CH:23]=[CH:22][C:19]([CH2:20][S:21][N:25]2[C:29](=[O:30])[CH2:28][CH2:27][C:26]2=[O:31])=[CH:18][CH:17]=1)([O-:15])=[O:14]
Reactant: O=C1CCC(=O)N1Br
Reactant: O=[N+]([O-])c1ccc(CS)cc1
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: CO
Solvent: O
Product: O=C1CCC(=O)N1SCc1ccc([N+](=O)[O-])cc1
Temperature: 50 °C
Reaction time: 1 h
Yield: 64.9 %

Procedure:
Lead (II) acetate trihydrate (0.759 g, 2.0 mmol) and 4-nitrobenzyl mercaptan (0.745 g, 4.4 mmol) were stirred together in methanol (24 cm3) solution at room temperature. After 1 h, the products were filtered and the residue was washed with a small volume of cold methanol. The residue was dried in vacuo over calcium chloride and then suspended in dry acetonitrile (20 cm3). Following the evaporation of the solvent under reduced pressure, the residue was suspended in dry benzene (20 cm3) and the solvent was again evaporated under reduced pressure. Finally, the residue was re-suspended in dry benzene (64 cm3) and N-bromosuccinimide (0.783 g, 4.4 mmol) was added in three portions over a period of 45 min to the stirred suspension at room temperature. The reactants were then heated at 50° C., under an atmosphere of argon, for 14 h. The cooled products were filtered and the filtrate was evaporated under reduced pressure to give a solid. The latter material was crystallized from ethyl acetate--hexane to give N-(4-nitrobenzylmercapto)succinimide 18 (0.76 g, 65%) (Found: C, 49.85; H, 3.8; N, 10.4. C11H10N2O4S requires: C, 49.6; H, 3.8; N, 10.5%), m.p. 146°-148° C.; δH [CDCl3 ] 2.73 (4 H, s), 4.18 (2 H, s), 7.50 (2 H, m), 8.17 (2 H, m); δC [CDCl3 ] 28.4, 40.5, 123.8, 130.3, 141.9, 147.5, 176.2.
Reaction SMILES: F[C@H]1CC[C@:5]2([C:20]3[CH:25]=[CH:24]C=CC=3F)[N:6]=[C:7]([NH:10]C(=O)OC(C)(C)C)[S:8][CH2:9][C@@H:4]2C1.Br[C:28]1[CH:33]=[C:32]([Cl:34])[CH:31]=[C:30]([Br:35])[CH:29]=1>>[Br:35][C:30]1[CH:29]=[C:28]([C@:5]23[CH2:20][CH2:25][CH2:24][C@H:4]2[CH2:9][S:8][C:7]([NH2:10])=[N:6]3)[CH:33]=[C:32]([Cl:34])[CH:31]=1
Reactant: Clc1cc(Br)cc(Br)c1
Reactant: CC(C)(C)OC(=O)NC1=N[C@@]2(c3ccccc3F)CC[C@H](F)C[C@H]2CS1
Product: NC1=N[C@@]2(c3cc(Cl)cc(Br)c3)CCC[C@H]2CS1

Procedure:
The title compound was synthesized from hex-5-enal oxime (JOC, 41 (5), 863-9; 1976) according to the method of Preparation Example 8, using 1,3-dibromo-5-chlorobenzene instead of 2-fluorobromobenzene.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[Se:11][CH:12]=[CH:13][CH:14]=2)=[CH:6][CH:5]=1)[CH2:2][CH3:3].[Li][CH2:16]CCC.CI.[Cl-].[NH4+].N>C(OCC)C>[CH3:16][C:12]1[Se:11][C:10]([C:7]2[CH:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][CH:6]=2)=[CH:14][CH:13]=1
Reactant: [Li]CCCC
Reactant: CCCc1ccc(-c2ccc[se]2)cc1
Agent: N
Agent: [Cl-]
Agent: [NH4+]
Solvent: CI
Solvent: CCOCC
Product: CCCc1ccc(-c2ccc(C)[se]2)cc1
Temperature: -70 °C
Reaction time: 3 h

Procedure:
3.0 g (12.0 mmol) of 2-(4-propylphenyl)selenophene are initially introduced in 30 ml of diethyl ether, and 9.4 ml (15.0 mmol, 15% soln. in hexane) of n-BuLi are metered in rapidly. The mixture is heated under reflux for 30 min and subsequently cooled to −70° C. 3.0 ml (48.2 mol) of methyl iodide are added in one portion, and the mixture is warmed to RT and stirred for 3 h. Sat. ammonium chloride soln. and conc. ammonia soln. are added, and the batch is stirred vigorously for a few minutes. The organic phase is separated off, and the aqueous phase is extracted with MTBE. The combined organic phases are washed with 2 N hydrochloric acid and sat. sodium chloride soln. and dried using sodium sulfate. The solution is concentrated to dryness, and the residue is purified by column chromatography (SiO2, n-heptane:EtOAc=20:1→10:1→5:1). The further purification is carried out by flash chromatography (SiO2 RP-18, ACN:water=9:1); 2-methyl-5-(4-propylphenyl)selenophene is obtained as a colourless solid (m.p. 31° C.).
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([O:10][C:11]3[CH:12]=[C:13]([NH:17][C:18](=[O:29])[C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=4)[CH:14]=[CH:15][CH:16]=3)=[N:6][N:5]2[CH:30]=1.C(N(CC)CC)C.[CH3:38][S:39](Cl)(=[O:41])=[O:40]>O1CCCC1>[CH3:38][S:39]([NH:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([O:10][C:11]3[CH:12]=[C:13]([NH:17][C:18](=[O:29])[C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=4)[CH:14]=[CH:15][CH:16]=3)=[N:6][N:5]2[CH:30]=1)(=[O:41])=[O:40]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1cn2nc(Oc3cccc(NC(=O)c4cccc(C(F)(F)F)c4)c3)ccc2n1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CS(=O)(=O)Nc1cn2nc(Oc3cccc(NC(=O)c4cccc(C(F)(F)F)c4)c3)ccc2n1
Yield: 60.7 %

Procedure:
Using N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-3-(trifluoromethyl)benzamide (150 mg, 0.362 mmol), triethylamine (76 μL, 0.544 mmol), methanesulfonyl chloride (34 μL, 0.435 mmol) and tetrahydrofuran (5 mL) as starting materials and in the same manner as in Example 388, the title compound (108 mg, 61%) was obtained as a pale-green-powder.
Reaction SMILES: [BH3-]C#N.[Na+].[NH2:5][CH2:6][CH:7]1[CH2:16][CH2:15][CH2:14][C:13]2[C:12]([O:17][C:18]3[CH:26]=[CH:25][C:21]([C:22]([NH2:24])=[O:23])=[CH:20][N:19]=3)=[CH:11][CH:10]=[CH:9][C:8]1=2.[C:27]1(=O)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>CC(O)=O.CO>[CH:27]1([NH:5][CH2:6][CH:7]2[CH2:16][CH2:15][CH2:14][C:13]3[C:12]([O:17][C:18]4[CH:26]=[CH:25][C:21]([C:22]([NH2:24])=[O:23])=[CH:20][N:19]=4)=[CH:11][CH:10]=[CH:9][C:8]2=3)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1
Reactant: O=C1CCCCC1
Reactant: NCC1CCCc2c(Oc3ccc(C(N)=O)cn3)cccc21
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: NC(=O)c1ccc(Oc2cccc3c2CCCC3CNC2CCCCC2)nc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 76.4 %

Procedure:
Add NaBH3CN (63 mg, 1.00 mmol) to a solution of 6-(5-aminomethyl-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-nicotinamide (intermediate 20, 148 mg, 0.500 mmol) and cyclohexanone (98 mg, 1.00 mmol) dissolved in 5% AcOH/MeOH (5 ml) and stir at ambient temperature for 16 hours. Concentrate the reaction mixture and redissolved in EtOAc. Wash the EtOAc solution with 5% aq. KOH and brine before drying (MgSO4) and concentrating. Purify on silica gel (5% (1N NH3/MeOH)/DCM) to obtain 145 mg of the title compound as a white foam. Mass spectrum (ion spray): m/z=380 (M+1); 1HNMR (CDCl3): 8.56 (s, 1H), 8.15 (d, 1H), 7.22-7.14 (m, 2H), 6.90 (m, 2H), 5.79 (br. s, 2H), 2.99 (m, 1H), 2.96-2.79 (m, 2H), 2.63-2.41 (m, 3H), 1.91 (m, 2H), 1.85-1.67 (m, 6H), 1.31-1.04 (m, 6H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([CH:12]=O)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[CH3:14][NH:15][S:16](Cl)(=[O:18])=[O:17].[BH4-].[Na+]>N1C=CC=CC=1>[CH3:14][N:15]1[S:16](=[O:18])(=[O:17])[NH:1][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][N:10]=3)[CH:5]=[CH:4][C:3]=2[CH2:12]1
Reactant: CNS(=O)(=O)Cl
Reactant: Nc1c(C=O)ccc2cccnc12
Agent: [BH4-]
Agent: [Na+]
Solvent: c1ccncc1
Product: CN1Cc2ccc3cccnc3c2NS1(=O)=O
Yield: 13.8 %

Procedure:
In a similar fashion using route 27 general procedure 70, 8-amino-quinoline-7-carbaldehyde (100 mg, 0.58 mmol), N-methylsulfamoyl chloride (226 mg, 1.74 mmol), NaBH4 (22 mg, 0.58 mmol) and pyridine (1 ml) gave the title compound (20 mg, 14%) after purification by column chromatography with heptane/EtOAc (90:10) as the eluent.