Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[C:10](I)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1.[CH3:27][O:28][C:29]1[CH:34]=[C:33](B(O)O)[CH:32]=[CH:31][N:30]=1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[C:10]([C:33]3[CH:32]=[CH:31][N:30]=[C:29]([O:28][CH3:27])[CH:34]=3)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1
Reactant: COc1cc(B(O)O)ccn1
Reactant: C[Si](C)(C)CCOCn1cc(I)c2c(OC3CCOCC3)nc(Cl)nc21
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: COc1cc(-c2cn(COCC[Si](C)(C)C)c3nc(Cl)nc(OC4CCOCC4)c23)ccn1
Temperature: 80 °C
Reaction time: 1.5 h
Yield: 71 %

Procedure:
To a degassed mixture of 2-chloro-5-iodo-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), (2-methoxypyridin-4-yl)boronic acid (2 equiv) and tripotassium phosphate trihydrate (3 equiv) in a 9:1 mixture of 1,4-dioxane and water (0.1 M) was added palladium 1,1-bis(diphenylphosphion)ferrocene dichloride (0.2 equiv). The reaction mixture was stirred at 80° C. for 1.5 h. After the reaction was complete, the reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography (15% ethyl acetate in petroleum ether) to afford the title compound (71% yield) as a white powder. MS (ESI) m/z 491.3 [M+1]+.
Reaction SMILES: Cl.[F:2][C:3]([F:34])([F:33])[C:4]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:5]=1[CH2:6][N:7]1[CH2:12][CH2:11][CH:10](/[CH:13]=[C:14]2/[C:15]([NH:20][CH2:21][C:22](O)=[O:23])=[N:16][C:17](=[O:19])[S:18]/2)[CH2:9][CH2:8]1.C(N(C(C)C)C(C)C)C.[CH3:44][O:45][CH2:46][CH2:47][NH:48][CH2:49][CH2:50][O:51][CH3:52].F[P-](F)(F)(F)(F)F.C(C(=NO[C+](N(C)C)N1CCOCC1)C(OCC)=O)#N>CN(C=O)C.O>[F:34][C:3]([F:2])([F:33])[C:4]1[CH:28]=[C:27]([C:29]([F:31])([F:32])[F:30])[CH:26]=[CH:25][C:5]=1[CH2:6][N:7]1[CH2:12][CH2:11][CH:10](/[CH:13]=[C:14]2/[C:15]([NH:20][CH2:21][C:22]([N:48]([CH2:49][CH2:50][O:51][CH3:52])[CH2:47][CH2:46][O:45][CH3:44])=[O:23])=[N:16][C:17](=[O:19])[S:18]/2)[CH2:9][CH2:8]1
Reactant: COCCNCCOC
Reactant: O=C(O)CNC1=NC(=O)S/C1=C\C1CCN(Cc2ccc(C(F)(F)F)cc2C(F)(F)F)CC1
Agent: CCOC(=O)C(C#N)=NO[C+](N(C)C)N1CCOCC1
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COCCN(CCOC)C(=O)CNC1=NC(=O)S/C1=C\C1CCN(Cc2ccc(C(F)(F)F)cc2C(F)(F)F)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 1.7 %

Procedure:
To a solution of N-[(5Z)-5-({1-[2,4-bis(trifluoromethyl)benzyl]piperidin-4-yl}methylidene)-2-oxo-2,5-dihydro-1,3-thiazol-4-yl]glycine hydrochloride (500 mg), N-ethyl-N-(1-methylethyl)propan-2-amine (0.49 mL) and 2-methoxy-N-(2-methoxyethyl)ethanamine (376 mg) in DMF (5 mL) was added (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (403 mg), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate) to give the title compound (10 mg).
Reaction SMILES: [F:1][B-:2]([F:5])([F:4])[F:3].[CH3:6][N:7]([CH3:34])[C:8]1[CH:33]=[CH:32][C:11]([CH:12]=[N:13][N+:14]2[CH:18]=[CH:17][N:16]([N:19]=[CH:20][C:21]3[CH:26]=[CH:25][C:24]([N:27]([CH3:29])[CH3:28])=[CH:23][CH:22]=3)[C:15]=2SC)=[CH:10][CH:9]=1.[NH3:35].CS.C(OCC)C>CN(C)C=O>[F:1][B-:2]([F:5])([F:4])[F:3].[NH2:35][C:15]1[N:14]([N:13]=[CH:12][C:11]2[CH:32]=[CH:33][C:8]([N:7]([CH3:34])[CH3:6])=[CH:9][CH:10]=2)[CH:18]=[CH:17][N+:16]=1[N:19]=[CH:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH3:29])[CH3:28])=[CH:23][CH:22]=1
Reactant: CSc1n(N=Cc2ccc(N(C)C)cc2)cc[n+]1N=Cc1ccc(N(C)C)cc1
Reactant: N
Agent: CS
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CN(C)c1ccc(C=Nn2cc[n+](N=Cc3ccc(N(C)C)cc3)c2N)cc1

Procedure:
0.99 g of 1,3-bis[[p-(dimethylamino)benzylidene]amino]-2-(methylthio)imidazolium tetrafluoroborate is dissolved in 15 ml of absolute dimethylformamide. Dry ammonia is conducted into the reaction solution at room temperature while stirring until the cleavage of methyl mercaptan is complete. The solution is treated with diethyl ether. The precipitate obtained is washed twice with water and twice with cold methanol and re-precipitated from dimethylformamide/diethyl ether. There is obtained yellow 2-amino-1,3-bis[[p-(dimethylamino)benzylidene]amino]imidazolium tetrafluoroborate with a decomposition point >260°.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[N:10]=[C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]3)[S:8][C:6]=2[N:7]=1.[CH3:28][N:29]([CH3:45])[C:30]1[N:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][N:31]=1>>[CH3:28][N:29]([CH3:45])[C:30]1[N:35]=[CH:34][C:33]([C:2]2[N:3]=[C:4]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[C:5]3[N:10]=[C:9]([CH2:11][N:12]4[CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]4)[S:8][C:6]=3[N:7]=2)=[CH:32][N:31]=1
Reactant: CN(C)c1ncc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: CS(=O)(=O)N1CCN(Cc2nc3c(N4CCOCC4)nc(Cl)nc3s2)CC1
Product: CN(C)c1ncc(-c2nc(N3CCOCC3)c3nc(CN4CCN(S(C)(=O)=O)CC4)sc3n2)cn1
Yield: 10.7 %

Procedure:
5-Chloro-2-(4-methanesulfonyl-piperazin-1-ylmethyl)-7-morpholin-4-yl-thiazolo[5,4-d]pyrimidine (80 mg) was reacted with 55 mg of dimethyl-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-yl]-amine via General Procedure A. The product was purified by reverse phase HPLC to yield 10.3 mg of 110. MS (Q1) 520.2 (M)+.
Reaction SMILES: [P:1](Cl)([S:6][CH2:7][CH2:8][CH3:9])([O:3][CH2:4][CH3:5])=[O:2].C(N(CC)CC)C.[OH:18][C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[CH:21]=[O:22]>C(Cl)Cl>[P:1]([O:18][C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[CH:21]=[O:22])([S:6][CH2:7][CH2:8][CH3:9])([O:3][CH2:4][CH3:5])=[O:2]
Reactant: O=Cc1ccccc1O
Reactant: CCCSP(=O)(Cl)OCC
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCSP(=O)(OCC)Oc1ccccc1C=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
The solution of O-ethyl S-propyl chlorothiophosphate prepared in Example 1 was cooled to 10° C. and triethylamine (1.629 grams; 0.016 mole) was added. A solution of 2-hydroxybenzaldehyde (1.95 grams; 0.016 mole) in methylene chloride (5 ml) was slowly added to the mixture while maintaining the temperature at about 0° C. After this addition was completed the temperature of the reaction mixture was allowed to rise to room temperature and stirring was continued for a period of one hour. After this time the reaction mixture was transferred into a separatory funnel and methylene chloride (100 ml) was added. The resulting solution was washed twice with water (100 ml), twice with aqueous sodium hydroxide (0.1 N; 50 ml) and again twice with water (100 ml). The washed solution was then dried over anhydrous magnesium sulfate, filtered and stripped of solvent under vacuum in a rotary evaporator leaving a light orange oil as the residue. This oil was placed under high vacuum for a period of one hour to yield the desired product as a yellow oil.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[CH2:7]([C:11]1[N:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=O)[CH2:8][CH2:9][CH3:10].Cl.[CH:22]12[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH:23]1[NH2:32])[CH2:29]2.C(N(C(C)C)C(C)C)C>ClCCl>[CH:22]12[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH:23]1[NH:32][C:13](=[O:15])[C:12]1[CH:16]=[CH:17][C:18]([Cl:20])=[N:19][C:11]=1[CH2:7][CH2:8][CH2:9][CH3:10])[CH2:29]2
Reactant: CCCCc1nc(Cl)ccc1C(=O)O
Reactant: NC1C2CC3CC(C2)CC1C3
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCCCc1nc(Cl)ccc1C(=O)NC1C2CC3CC(C2)CC1C3
Temperature: 25 °C
Reaction time: 4 h
Yield: 83.6 %

Procedure:
A solution of oxalyl chloride (0.105 mL, 1.20 mmol) in dichloromethane (2 mL) was added dropwise to a stirred suspension of 2-butyl-6-chloronicotinic acid (214 mg, 1.00 mmol), in dichloromethane (25 mL) over a period of 2 minutes under nitrogen. The resulting solution was stirred at room temperature for 4 hours. The reaction mixture was evaporated to dryness and dissolved in DCM (5 mL). This solution was added dropwise to a stirred solution of 2-adamantanamine hydrochloride (188 mg, 1.00 mmol) and N-ethyldiisopropylamine (0.693 mL, 4.01 mmol) in dichloromethane (20 mL) over a period of 2 minutes under nitrogen. The resulting solution was stirred at room temperature for 16 hours. The reaction mixture was diluted with DCM (20 mL), and washed sequentially with 0.1M HCl (20 mL), saturated NaHCO3 (20 mL), and saturated brine (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford N-adamantan-2-yl-2-butyl-6-chloronicotinamide (290 mg, 83%)
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[N:17][S:18]([CH3:21])(=[O:20])=[O:19])OC2C=CC=CC=2)[CH:5]=[CH:6][CH:7]=1.[CH3:22][C:23]1[C:31]2[C:30]([N:32]3[CH2:37][CH2:36][NH:35][C@@H:34]([CH3:38])[CH2:33]3)=[N:29][CH:28]=[N:27][C:26]=2[NH:25][CH:24]=1.C(N(CC)CC)C>CC#N>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([N:35]2[CH2:36][CH2:37][N:32]([C:30]3[C:31]4[C:23]([CH3:22])=[CH:24][NH:25][C:26]=4[N:27]=[CH:28][N:29]=3)[CH2:33][C@@H:34]2[CH3:38])=[N:17][S:18]([CH3:21])(=[O:19])=[O:20])[CH:5]=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)N=C(Nc1cccc(Br)c1)Oc1ccccc1
Reactant: Cc1c[nH]c2ncnc(N3CCN[C@@H](C)C3)c12
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1c[nH]c2ncnc(N3CCN(C(=NS(C)(=O)=O)Nc4cccc(Br)c4)[C@@H](C)C3)c12

Procedure:
The carbamimidate from step B (100 mg, 0.27 mmol), (S)-5-methyl-4-(3-methylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine, from Example 1, step B (63 mg, 0.27 mmol), and triethylamine (77 μl, 0.27 mmol) were combined in MeCN (1.5 ml) and heated to reflux for 2 hours. The mixture was concentrated and purified by preparative HPLC to afford (S)—N-(3-bromophenyl)-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N′-(methylsulfonyl)piperazine-1-carboximidamide.
Reaction SMILES: O.[Sn](Cl)Cl.[Cl:5][C:6]1[CH:21]=[C:20]([Cl:22])[C:9]([C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[O:11])=[C:8]([N+:23]([O-])=O)[C:7]=1[OH:26].CCO.C([O-])(O)=O.[Na+]>CC(O)=O>[NH2:23][C:8]1[C:7]([OH:26])=[C:6]([Cl:5])[CH:21]=[C:20]([Cl:22])[C:9]=1[C:10]([NH:12][C:13]1[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=1)=[O:11]
Reactant: O=C(Nc1ccc(F)cc1)c1c(Cl)cc(Cl)c(O)c1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Solvent: O
Product: Nc1c(O)c(Cl)cc(Cl)c1C(=O)Nc1ccc(F)cc1
Temperature: 70 °C
Yield: 79.3 %

Procedure:
A suspension of tin (II) chloride hydrate (8.8 g, 0.039 mol), 4,6-dichloro-N-(4-fluorophenyl)-3-hydroxy-2-nitrobenzamide (2.7 g, 0.008 mol) and EtOH (70 mL) was heated at 70° C. for 1 h and left to cool to room temperature. The mixture was poured onto ice, basified to pH 8 (sat'd NaHCO3), and stirred at room temperature for 1.5 h before re-acidifying to pH 6.5 with glacial HOAc. The suspension was filtered; the filtrate was concentrated to give a beige solid. The beige solid was combined with the filter cake and extracted with hot ethyl acetate (5×). The extracts were combined to provide 2-amino-4,6-dichloro-N-(4-fluorophenyl)-3-hydroxybenzamide as a solid (2.0 g, 79%).
Reaction SMILES: [N:1]([CH2:4][Si:5]([CH3:8])([CH3:7])[CH3:6])=[N+:2]=[N-:3].[CH2:9]([O:11][CH:12]([O:15][CH2:16][CH3:17])[C:13]#[CH:14])[CH3:10].[Na].C(O)CCC.O>O>[CH2:9]([O:11][CH:12]([O:15][CH2:16][CH3:17])[C:13]1[N:3]=[N:2][N:1]([CH2:4][Si:5]([CH3:8])([CH3:7])[CH3:6])[CH:14]=1)[CH3:10]
Reactant: C#CC(OCC)OCC
Reactant: C[Si](C)(C)CN=[N+]=[N-]
Agent: [Na]
Solvent: CCCCO
Solvent: O
Product: CCOC(OCC)c1cn(C[Si](C)(C)C)nn1
Temperature: 25 °C
Reaction time: 16 h
Yield: 81.3 %

Procedure:
To a 100 ml round bottom flask equipped with a magnetic stir bar were added (azidomethyl)(trimethyl)silane (1.000 g, 7.740 mmol), 3,3-diethoxyprop-1-yne (0.992 g, 7.740 mmol), freshly made 1.0N sodium asorbate (0.774 ml, 7.740 mmol), and 1.0N Cu2SO4 (0.774 ml, 7.740 mmol) into 30.0 ml of a mixed solvent BuOH/H2O (1:1). The resulting solution was stirred at room temperature for 16 hours. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum to give the crude title compound as a light yellow liquid (1.620 g, 81% crude). ES-MS [M+1]+: 258.1 (M+H). This intermediate was carried over to the next step without further purifications and characterizations.
Reaction SMILES: CCN(C(C)C)C(C)C.[Cl:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[O:42]=[C:43]([N:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1)[CH2:44][NH:45][C:46]([C:48]1[CH:53]=[CH:52][C:51]([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[CH:50][CH:49]=1)=[O:47]>CN(C=O)C.O>[Cl:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([N:63]1[CH2:62][CH2:61][N:60]([C:43](=[O:42])[CH2:44][NH:45][C:46]([C:48]2[CH:53]=[CH:52][C:51]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[CH:50][CH:49]=2)=[O:47])[CH2:65][CH2:64]1)=[O:15]
Reactant: O=C(NCC(=O)N1CCNCC1)c1ccc(-c2ccccc2)cc1
Reactant: O=C(O)c1ccccc1Cl
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: O=C(NCC(=O)N1CCN(C(=O)c2ccccc2Cl)CC1)c1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 38.3 %

Procedure:
DIPEA (149.8 mg, 1.15 mmol) was added to a stirred solution of 2-chloro-benzoic acid (40.3 mg, 0.26 mmol) in DMF (3 mL), HOBt (38.2 mg, 0.28 mmol) and EDCI.HCl (123.4 mg, 0.64 mmol) at room temperature. After 2 minutes biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide (100 mg, 0.31 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added, and the resulting precipitate was filtered. The residue was purified by column chromatography (using 60-120 mesh silica gel and 60% EtOAc in hexane as eluent) to afford 46 mg (38.6% yield) of biphenyl-4-carboxylicacid {2-[4-(2-chloro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide, LC-MS purity: 99.47%, 1H NMR: (DMSO) δ 8.7-8.6 (bs, 1H), 8.02-7.92 (d, 2H), 7.84-7.7 (q, 4H), 7.6-7.38 (m, 7H), 4.24 (d, 1H), 4.18 (d, 1H), 3.8-3.6 (m, 4H), 3.56-3.46 (m, 2H), 3.26-3.12 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[CH3:12][N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])([O-])=O.[Na+].[Na+]>ClC(Cl)C>[F:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:3]=1[CH2:4][N:16]1[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][CH2:15]1
Reactant: CN1CCNCC1
Reactant: COc1ccc(C=O)c(F)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: COc1ccc(CN2CCN(C)CC2)c(F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 100.1 %

Procedure:
2-Fluoro-4-methoxybenzaldehyde (6.0 g, 39 mmol) was dissolved in dichloroethane (100 mL) and 1-methylpiperazine (4.5 g, 45 mmol) was added and the solution was stirred at rt for 30 minutes. Sodium triacetoxyborohydride (10 g, 47 mmol) was added in portions and the reaction mixture was stirred at rt over night. Aqueous Na2CO3 (sat.) was added to the reaction and the phases were separated. The aqueous phase were extracted twice with DCM and the combined organic phases were filtered through a phase separator and the solvent was removed by evaporation. There was obtained 9.3 g (100%) of 29A as a brown oil. 1H NMR (500 MHz, CDCl3): δ 2.28 (s, 3H), 2.30-2.70 (bm, 8H), 3.53 (s, 2H), 3.78 (s, 3H), 6.53-6.71 (m, 2H), 7.17-7.27 (m, 1H).
Reaction SMILES: B.[CH3:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([CH3:12])[C:10]=1[OH:11])[C:6]#[N:7].[ClH:13]>O1CCCC1>[ClH:13].[NH2:7][CH2:6][C:5]1[CH:4]=[C:3]([CH3:2])[C:10]([OH:11])=[C:9]([CH3:12])[CH:8]=1
Reactant: Cc1cc(C#N)cc(C)c1O
Agent: B
Agent: Cl
Solvent: C1CCOC1
Product: Cc1cc(CN)cc(C)c1O
Temperature: 25 °C

Procedure:
A solution of borane in tetrahydrofuran (27.1 ml of a 1M solution, 27.1 mmol) was added dropwise to a solution of 3,5-dimethyl-4-hydroxybenzonitrile (1.0 g, 6.79 mmol) in tetrahydrofuran (70 ml) and the resulting solution heated to reflux under a nitrogen atmosphere for 16 hours. The reaction was cooled to room temperature and treated with 6N hydrochloric acid (20 ml) and refluxed for a further 30 minutes. The reaction mixture was cooled to room temperature and the solvent removed in vacuo. Purification using strong cation exchange resin, eluting biproducts with methanol followed by 2M ammonia in methanol to elute the product gave the title compound as an orange oil. The oil was treated with 1M hydrogen chloride in methanol (20 ml) and the solvent removed in vacuo to give the title compound as a pale yellow solid (1.12 g).
Reaction SMILES: [NH2:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][SH:4].[C:8]([S:11][CH2:12][CH2:13][N+:14]([CH3:17])([CH3:16])[CH3:15])(=[O:10])[CH3:9]>>[SH:11][CH2:12][CH2:13][N+:14]([CH3:17])([CH3:16])[CH3:15].[C:8]([NH:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][SH:4])(=[O:10])[CH3:9]
Reactant: N[C@@H](CS)C(=O)O
Reactant: CC(=O)SCC[N+](C)(C)C
Product: CC(=O)N[C@@H](CS)C(=O)O
Product: C[N+](C)(C)CCS

Procedure:
reacting the cysteine with the acetylthiocholine to form thiocholine and N-acetylcysteine, each in a concentration of about 0.2 molar to about 3.0 molar and in a molar ratio of thiocholine to N-acetylcysteine of 1:1.2 to 1.2:1.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]#[N:5].C([OH:8])C.[ClH:9].[CH2:10]([O:12][CH2:13]C)C>>[ClH:9].[CH3:10][O:12][CH2:13][C:1]([O:2][CH2:3][CH:4]=[NH:5])=[O:8]
Reactant: COCC#N
Reactant: CCO
Reactant: CCOCC
Agent: Cl
Product: COCC(=O)OCC=N

Procedure:
A solution of 35.5 g (0.50 mol) of methoxyacetonitrile in 29 ml (23 g, 0.50 mol) of ethanol and 30 ml of absolute diethylether was cooled to 0° C. and over 1 hour 22.5 g (0.62 mol) of hydrogen chloride gas was introduced, whilst towards the end of the introduction of gas the reaction product crystallised out. To complete the precipitation 130 ml of diethylether were added and the colourless needles were filtered off.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=2[Cl:23])(O)[CH2:9][N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)=[N:6][CH:7]=1.N1C=CN=C1.S(Cl)([Cl:31])=O>C(#N)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([Cl:31])([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=2[Cl:23])[CH2:9][N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)=[N:6][CH:7]=1
Reactant: O=S(Cl)Cl
Reactant: OC(Cn1cncn1)(c1ccc(Cl)cn1)c1ccc(Cl)cc1Cl
Agent: c1c[nH]cn1
Solvent: CC#N
Product: Cl
Product: Clc1ccc(C(Cl)(Cn2cncn2)c2ccc(Cl)cc2Cl)nc1
Reaction time: 18 h

Procedure:
1-(5-Chloropyrid-2-yl)-1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanol (750 mg, 2.03 mmoles) and imidazole (840 mg, 12.35 mmoles) were stirred in 30 ml of acetonitrile while 720 mg of thionyl chloride was added. The reaction mixture was stirred for 18 hrs. at room temperature and the solvent was then evaporated. Dilute sodium bicarbonate solution (10 ml) was added to the residue and the mixture extracted with ethyl acetate (4×20 ml). The combined extracts were dried over magnesium sulfate, evaporated under vacuum and the residue chromatographed on 230-400 mesh silica gel using ethyl acetate-petrol (b.p. 60°-80° C.) (1:1, v:v). The fractions containing the product were combined and concentrated to dryness to give the product as a colorless gum. Treatment of the residue with ethereal hydrogen chloride gave the hydrochloride salt which was recrystallized from methanol-diisopropyl ether, 240 mg (28% yield), m.p. 120°-140° C.
Reaction SMILES: [O:1]=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[NH:7][C:6](=[O:12])[CH:5]=[CH:4][C:3]1=2.[H-].[Li+].Br[CH2:16][CH:17]=[CH2:18]>CN(C)C=O>[O:1]=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[N:7]([CH2:18][CH:17]=[CH2:16])[C:6](=[O:12])[CH:5]=[CH:4][C:3]1=2
Reactant: O=C1CCCc2[nH]c(=O)ccc21
Reactant: C=CCBr
Agent: [H-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: C=CCn1c2c(ccc1=O)C(=O)CCC2
Temperature: 25 °C
Reaction time: 3 h
Yield: 63 %

Procedure:
A mixture of 5,6,7,8-tetrahydro-5-oxo-2(1H)-quinolinone (20.0 g), lithium hydride (1.57 g), and dimethylformamide (800 ml) was stirred for 3 hrs at 25° C., under nitrogen. 3-Bromopropene (15.5 g) was added and the mixture was stirred for an additional eighteen hrs. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was triturated with petroleum ether to afford 15.7 g (63%) of 5,6,7,8-tetrahydro-5-oxo-1-(2-propenyl)-2(1H)-quinolinone.
Reaction SMILES: [CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9](F)=[C:8]([Cl:13])[CH:7]=1)(=[O:5])=[O:4])[CH3:2].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]([OH:24])=[O:23])=[CH:17][C:16]=1[OH:25]>>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]([OH:24])=[O:23])=[CH:17][C:16]=1[O:25][C:9]1[CH:10]=[CH:11][C:6]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[CH:7][C:8]=1[Cl:13]
Reactant: O=C(O)Cc1ccc(Cl)c(O)c1
Reactant: CCS(=O)(=O)c1ccc(F)c(Cl)c1
Product: CCS(=O)(=O)c1ccc(Oc2cc(CC(=O)O)ccc2Cl)c(Cl)c1

Procedure:
The title compound was prepared by the method of example 2 step (iii) using the product of step (i) and the product of example 1 step (iii).
Reaction SMILES: [F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][N:7]([CH2:14][CH2:15][N:16]([CH3:23])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][NH2:22])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][CH:3]=1.[C:26](N1C=CN=C1)(N1C=CN=C1)=[O:27].[N:38]1([CH2:44][C:45]2[CH:46]=[C:47]([CH:53]=[CH:54][CH:55]=2)[O:48][CH2:49][CH2:50][CH2:51][NH2:52])[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1>>[F:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][N:7]([CH2:14][CH2:15][N:16]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][NH:22][C:26]([NH:52][CH2:51][CH2:50][CH2:49][O:48][C:47]2[CH:53]=[CH:54][CH:55]=[C:45]([CH2:44][N:38]3[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]3)[CH:46]=2)=[O:27])[CH3:23])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: NCCCOc1cccc(CN2CCCCC2)c1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CN(CCCCCN)CCN(Cc1ccc(F)cc1)c1ccccn1
Product: CN(CCCCCNC(=O)NCCCOc1cccc(CN2CCCCC2)c1)CCN(Cc1ccc(F)cc1)c1ccccn1

Procedure:
Preparation is effected analogously to Example 63, using 0.51 g (1.5 mmol) of N-[2-[N-(4-fluorobenzyl)-N-(2-pyridyl)amino]ethyl]-N-methyl-1,5-pentanediamine and the equimolar amounts of 1,1'-carbonyldiimidazole and 3-[3-(piperidinomethyl)phenoxy]propylamine as starting materials. Working up by chromatography analogously to Example 63 yields the purified title compound in the form of a viscous oil; MS (+FAB method): m/z (rel. int. [%])=619 ([M+H]+, 3), 77 (100); IR (KBr): 1634 cm-1 (C=O). For further analysis, a portion of the compound is converted into the tartaric acid salt and recrystallised from isopropanol/ether/petroleum ether; m.p.: 63° C. (isopropanol/ether/petroleum ether).