Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([O:14][C:15]([C:17]1([O:22]/[N:23]=[C:24](/[C:28]2[N:29]=[C:30]([NH:33][C:34]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[S:31][CH:32]=2)\[C:25](O)=[O:26])[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:53][CH:54]1[C:79](=[O:80])[N:56]2[C:57]([C:63]([O:65][CH:66]([C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=3)[C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=3)=[O:64])=[C:58]([CH2:61][Cl:62])[CH2:59][S:60][C@H:55]12.CN(C)C1C=CC=CC=1.P(Cl)(Cl)(Cl)=O>C(Cl)Cl.O.C(Cl)(Cl)Cl>[CH:1]([O:14][C:15]([C:17]1([O:22]/[N:23]=[C:24](/[C:28]2[N:29]=[C:30]([NH:33][C:34]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[S:31][CH:32]=2)\[C:25]([NH:53][CH:54]2[C:79](=[O:80])[N:56]3[C:57]([C:63]([O:65][CH:66]([C:67]4[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=4)[C:73]4[CH:74]=[CH:75][CH:76]=[CH:77][CH:78]=4)=[O:64])=[C:58]([CH2:61][Cl:62])[CH2:59][S:60][C@H:55]23)=[O:26])[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:16])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CCl)CS[C@H]12
Reactant: O=C(O)/C(=N\OC1(C(=O)OC(c2ccccc2)c2ccccc2)CCCC1)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Solvent: CN(C)c1ccccc1
Solvent: O
Solvent: O=P(Cl)(Cl)Cl
Product: O=C(OC(c1ccccc1)c1ccccc1)C1=C(CCl)CS[C@@H]2C(NC(=O)/C(=N\OC3(C(=O)OC(c4ccccc4)c4ccccc4)CCCC3)c3csc(NC(c4ccccc4)(c4ccccc4)c4ccccc4)n3)C(=O)N12
Reaction time: 4 h

Procedure:
2.12 g (3 mmol) of (Z)-2-(1-benzhydryloxycarbonyl-1-cyclopentyloxyimino)-2-(2-tritylaminothiazol-4-yl) acetic acid and 1.24 g (3 mmol) of benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate were dissolved in 50 ml of methylene chloride, and 1.2 ml (9.6 mmol) of N,N-dimethylaniline was added under cooling with ice. Then, 0.29 ml (3.15 mmol) of phosphorus oxychloride was dropwise added thereto, and the mixture was stirred at the same temperature for 4 hours. 30 ml of chloroform and 30 ml of water was added to the reaction solution. The organic layer was washed with water and with a saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate and concentrated to obtain the residue of the above identified compound, which was used for the subsequent reaction without purification.
Reaction SMILES: [OH:1][CH2:2][C:3]1([CH2:6][O:7][C:8]2[C:13]([O:14][CH3:15])=[C:12]([O:16][CH3:17])[CH:11]=[CH:10][C:9]=2[C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[CH2:20][CH2:21][C:22]3=[O:27])[CH2:5][CH2:4]1.C(N(CC)CC)C.[CH2:35]([N:42]=[C:43]=[O:44])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.COC1C(OC)=CC=C(C2C=CC=C3C=2CCC3=O)C=1OCC1(COC(=O)NCC)CC1>ClCCl>[CH3:15][O:14][C:13]1[C:12]([O:16][CH3:17])=[CH:11][CH:10]=[C:9]([C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[CH2:20][CH2:21][C:22]3=[O:27])[C:8]=1[O:7][CH2:6][C:3]1([CH2:2][O:1][C:43](=[O:44])[NH:42][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:4][CH2:5]1
Reactant: O=C=NCc1ccccc1
Reactant: COc1ccc(-c2cccc3c2CCC3=O)c(OCC2(CO)CC2)c1OC
Agent: CCNC(=O)OCC1(COc2c(-c3cccc4c3CCC4=O)ccc(OC)c2OC)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(-c2cccc3c2CCC3=O)c(OCC2(COC(=O)NCc3ccccc3)CC2)c1OC

Procedure:
To a stirring solution of 4-[2-(1-Hydroxymethyl-cyclopropylmethoxy)-3,4-dimethoxy-phenyl]-indan-1-one (Compound 177) (150 mg, 0.407 mmol) in dichloromethane (15 mL), were added triethylamine (123 mg, 1.222 mmol) and benzyl isocyanate (105 mg, 0.812 mmol) and the resultant reaction mixture was subjected to the conditions used in the preparation of Compound 179 to afforded the title compound as a solid.
Reaction SMILES: CC1C=C(C=C(C)C=1)N.[S-]C#N.[NH4+].[CH3:14][C:15]1[CH:16]=[C:17]([NH:22][C:23]([NH2:25])=[S:24])[CH:18]=[C:19]([CH3:21])[CH:20]=1.BrBr.[NH2:28][C:29]1[S:30][C:31]2[C:37]([CH3:38])=[CH:36][C:35]([CH3:39])=[CH:34][C:32]=2[N:33]=1.[Na].C(O[CH:44]=[C:45]([C:48]#[N:49])[C:46]#[N:47])C>C(O)C.C(Cl)(Cl)Cl>[NH2:25][C:23]1[S:24][C:18]2[C:19]([CH3:21])=[CH:20][C:15]([CH3:14])=[CH:16][C:17]=2[N:22]=1.[CH3:39][C:35]1[CH:36]=[C:37]([CH3:38])[C:31]2[S:30][C:29]([N:28]=[C:44]=[C:45]([C:48]#[N:49])[C:46]#[N:47])=[N:33][C:32]=2[CH:34]=1
Reactant: CCOC=C(C#N)C#N
Reactant: Cc1cc(C)cc(NC(N)=S)c1
Agent: BrBr
Agent: Cc1cc(C)c2sc(N)nc2c1
Agent: Cc1cc(C)cc(N)c1
Solvent: CCO
Solvent: ClC(Cl)Cl
Product: Cc1cc(C)c2sc(N=C=C(C#N)C#N)nc2c1
Yield: 72.7 %

Procedure:
2-Amino-5,7-dimethylbenzothiazole was prepared by treatment of 3,5-dimethylaniline with ammonium thiocyanate and conversion of the resulting N-(3,5-dimethylphenyl)thiourea with bromine and chloroform (Barnikow and Bodeker Ber. 100(5), 1394), m.p. 142°-144°. 2-Amino-5,7-dimethylbenzothiazole, 6.16 g. (34.5 millimoles) was added to a solution of a pea-sized piece of sodium in 40 ml. of anhydrous ethanol. Ethoxymethylenemalononitrile, 4.22 g. (34.5 millimoles), was added to the solution and the mixture was heated at reflux for about 2 hrs. The precipitated solid was collected by filtration, washed with ethanol, and dried in vacuo at 100°, yielding 6.93 g. (72.7%) of the desired product which was a yellow solid, m.p. 239°-241°. A small portion was recrystallized from 95% ethanol and submitted for analysis, m.p. 241°-243°.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.[F:11][C:12]([F:21])([F:20])[C:13]1[CH:14]=[C:15]([CH:17]=[CH:18][CH:19]=1)[NH2:16].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH:16][C:15]1[CH:17]=[CH:18][CH:19]=[C:13]([C:12]([F:11])([F:20])[F:21])[CH:14]=1)=[O:7]
Reactant: O=C(O)c1cccc(Br)c1
Reactant: Nc1cccc(C(F)(F)F)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1cccc(C(F)(F)F)c1)c1cccc(Br)c1
Temperature: 25 °C
Reaction time: 22 h

Procedure:
A mixture of 3-bromobenzoic acid (500 mg, 2.49 mmol), 3-(trifluoromethyl)aniline (0.31 ml, 2.49 mmol) and DIEA (2.06 ml, 12.45 mmol) in DMF (6 ml) was treated with HATU (1.04 g, 2.74 mmol) and the reaction mixture was stirred at room temperature for 22 hours. The reaction mixture was partitioned between ethyl acetate and water and the organic phase was washed with sat'd NaCl(aq.), dried (MgSO4), filtered, and concentrated. Elution through a flash column (silica gel 60, 230-400 mesh, 4:1 hexanes:EtOAc) gave a yellow oil which solidified on standing (622 mg, 73%).
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:8][CH:9]=1)=[O:4].[OH-].[Na+].Cl>CO.O1CCCC1>[C:10]1([C:7]2[S:6][C:5]([C:3]([OH:4])=[O:2])=[CH:9][CH:8]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: COC(=O)c1ccc(-c2ccccc2)s1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1ccc(-c2ccccc2)s1
Reaction time: 2 h
Yield: 97.1 %

Procedure:
To a solution of 2-methoxycarbonyl-5-phenylthiophene (437 mg) in methanol (5 ml) and tetrahydrofuran (5 ml) was added an aqueous solution of sodium hydroxide (IN, 3 ml) followed by stirring for 2 hours. To the mixture was added hydrochloric acid (IN, 5 ml). The precipitate was collected by filtration and dried to give 5-phenylthiophene-2-carboxylic acid (397 mg, 97.1%).
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]([Cl:9])([Cl:8])[Cl:7])=[O:3].[NH2:10][C:11]1[N:15]([C:16]2[CH:17]=[C:18]([S:22][CH2:23][CH2:24][OH:25])[CH:19]=[CH:20][CH:21]=2)[N:14]=[C:13]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:12]=1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:7][C:6]([Cl:9])([Cl:8])[CH2:5][O:4][C:2](=[O:3])[NH:10][C:11]1[N:15]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([S:22][CH2:23][CH2:24][OH:25])[CH:17]=2)[N:14]=[C:13]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:12]=1
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Reactant: CC(C)(C)c1cc(N)n(-c2cccc(SCCO)c2)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(C)(C)c1cc(NC(=O)OCC(Cl)(Cl)Cl)n(-c2cccc(SCCO)c2)n1
Reaction time: 3 h
Yield: 100 %

Procedure:
Trichloroethyl chloroformate (0.1 mL, 0.78 mmol) was added to a solution of Intermediate 3b (176 mg, 0.60 mmol) and DIPEA (0.31 mL, 1.81 mmol) in THF (10 mL), and the mixture stirred for 3 h. The mixture was then partitioned between water (15 mL) and EtOAc (3×20 mL), and the combined organic extracts dried (Na2SO4) and concentrated in vacuo. The residue was triturated (cyclohexane) and filtered to give the title compound as a yellow solid (280 mg, 100%). LCMS (Method 1): Rt 3.93 min, m/z 466/468 [MH+]
Reaction SMILES: [C:1]([C:4]1[C:13](=[O:14])[C:12]2[C:7](=[C:8]([Br:15])[CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1)(=[O:3])[CH3:2].[C:16]([O-])([O-])=O.[K+].[K+].IC>CN(C)C=O>[C:1]([C:4]1[C:13](=[O:14])[C:12]2[C:7](=[C:8]([Br:15])[CH:9]=[CH:10][CH:11]=2)[N:6]([CH3:16])[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1c[nH]c2c(Br)cccc2c1=O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CC(=O)c1cn(C)c2c(Br)cccc2c1=O
Temperature: 90 °C
Reaction time: 2 h
Yield: 60.4 %

Procedure:
A mixture of 3-acetyl-8-bromoquinolin-4(1H)-one (5.35 g, 20.11 mmol) and K2CO3 (9.17 g, 66.3 mmol) in dry N,N-dimethylformamide (100 mL) was heated at 90° C. for 30 min. After cooling to room temperature, iodomethane (3.77 mL, 60.3 mmol) was added and the mixture was stirred again at 90° C. for 2 h. Then the reaction mixture was concentrated and diluted with water (50 mL), extracted with dichloromethane (4×50 mL), dried over sodium sulfate and absorbed onto silica gel. Purification by automatic silica gel column chromatography (Combiflash RF) eluting with ethyl acetate/hexanes (10-100%) afforded 3-acetyl-8-bromo-1-methylquinolin-4(1H)-one (3.4 g, 12.14 mmol, 60.4% yield) as a brown solid. LCMS: (M+H)+: 279.9.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10](=[O:22])[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=2)=[CH:4][CH:3]=1.O>P(=O)(O)(O)O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=3)[CH:11]=[C:10]([OH:22])[CH:9]=2)=[CH:4][CH:3]=1
Reactant: COc1ccc(CC(=O)CC(=O)c2ccc(Br)cc2)cc1OC
Agent: O=P(O)(O)O
Solvent: O
Product: COc1cc2cc(O)cc(-c3ccc(Br)cc3)c2cc1OC
Yield: 89.1 %

Procedure:
1-(4-Bromophenyl)-4-(3,4-dimethoxyphenyl)butane-1,3-dione (3 g, 8 mmol) in 85% phosphoric acid was heated at 70° C. for 20 h. The resulting solution was cooled, poured into water (150 ml) and filtered. The residue was dissolved in dichloromethane (50 ml), washed with water (50 ml), dried (MgSO4) and the solvent was removed under reduced pressure to give the title compound (2.56 g, 90%) as a brown powder.
Reaction SMILES: [P:1]([O:6]C)([O:4][CH3:5])[O:2][CH3:3].[CH2:8](Cl)[CH:9]=[CH2:10].CCl>[Ni]>[CH3:3][O:2][P:1]([CH2:10][CH:9]=[CH2:8])(=[O:6])[O:4][CH3:5]
Reactant: C=CCCl
Reactant: COP(OC)OC
Agent: [Ni]
Agent: CCl
Product: C=CCP(=O)(OC)OC

Procedure:
124 parts of trimethyl phosphite, together with 1 part of Raney nickel, are heated for 1 hour to 130°-140° C in a nitrogen atmosphere. 80 parts of allyl chloride are then slowly added dropwise so that the temperature does not fall below 80° to 90° C. The methyl chloride formed escapes through the reflux condenser. The reaction is over after 22 hours. The Raney nickel is filtered off, followed by fractionation in vacuo. Bp: 83°-84° C/12 Torr; nD20 : 1.4371; Yield: 86 parts, corresponding to 57% of the theoretical.
Reaction SMILES: [F:1][C:2]1[C:11]([N:12]2[CH2:16][CH2:15][CH2:14][C:13]2=[O:17])=[CH:10][C:9]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH:28](=O)[CH3:29]>>[CH2:28]([N:18]([CH2:19][C:20]1[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=1)[C:9]1[CH:10]=[C:11]([N:12]2[CH2:16][CH2:15][CH2:14][C:13]2=[O:17])[C:2]([F:1])=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5])[CH3:29]
Reactant: CC=O
Reactant: COC(=O)c1cc(NCc2ccc(OC)cc2)cc(N2CCCC2=O)c1F
Product: CCN(Cc1ccc(OC)cc1)c1cc(C(=O)OC)c(F)c(N2CCCC2=O)c1

Procedure:
Methyl 5-(ethyl{[4-(methyloxy)phenyl]methyl}amino)-2-fluoro-3-(2-oxo-1-pyrrolidinyl)benzoate (D155) was prepared from methyl 2-fluoro-5-({[4-(methyloxy)phenyl]methyl}amino)-3-(2-oxo-1-pyrrolidinyl)benzoate (D154) in an analogous manner to the process described for Ester 35 (B35) using acetaldehyde instead of propionaldehyde. [M+H]+=401.4, RT=3.11 min.
Reaction SMILES: [CH3:1][N:2]1[C:6]2=[N:7][C:8]([CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:9][C:10]([CH3:11])=[C:5]2[CH2:4][CH2:3]1.[Br:17]N1C(C)(C)C(=O)N(Br)C1=O>C(Cl)(Cl)Cl>[Br:17][C:9]1[C:10]([CH3:11])=[C:5]2[CH2:4][CH2:3][N:2]([CH3:1])[C:6]2=[N:7][C:8]=1[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCc1cc(C)c2c(n1)N(C)CC2
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Solvent: ClC(Cl)Cl
Product: CCCCCc1nc2c(c(C)c1Br)CCN2C
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 108 mg (0.50 mmol) of 1,4-dimethyl-6-pentyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine in 3 mL of chloroform was added 70.7 mg (0.25 mmol) of 1,3-dibromo-5,5-dimethylhydantoin in portions at 0° C. The reaction mixture was stirred at 0° C. for 30 min. The reaction was quenched by the addition of 5 mL of sat aq. NaHCO3. The mixture was extracted with chloroform and the combined organic layer was washed with brine and dried over MgSO4. The concentrated residue was purified by flash chromatography on a silica gel column (20 1.7 cm). Elution with 100:1 hexanes/ethyl acetate gave the product as a yellow oil: yield 136 mg (92%); silica gel TLC Rf 0.65 (8:1:1 hexanes/ethyl acetate/methanol); 1H NMR (CDCl3) δ 0.89 (t, 3H, J=7.2 Hz), 1.33-1.38 (m, 4H), 1.66 (quint, 2H, J=7.6 Hz), 2.16 (s, 3H), 2.77 (t, 2H, J=8.0 Hz), 2.82-2.87 (m, 5H) and 3.40 (t, 2H, J=8.0 Hz); 13C NMR (CDCl3) δ 14.1, 19.5, 22.6, 25.2, 28.4, 31.8, 33.0, 38.1, 52.4, 110.9, 120.4, 141.1, 156.8 and 161.8; mass spectrum, m/z 297.1 and 299.1 (M+H)+ (theoretical 297.1 and 299.1); mass spectrum (APCI), m/z 297.0968 and 199.0937 (M+H)+ (C14H22N2Br requires 297.0966 and 299.0946).
Reaction SMILES: [CH2:1]([C@H:8]1[C@@H:12]([C:13](O)=[O:14])[O:11][C:10](=[O:16])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[BH4-].[Na+].Cl>C(O)C.O>[CH2:1]([C@H:8]1[C@@H:12]([CH2:13][OH:14])[O:11][C:10](=[O:16])[NH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1N[C@@H](Cc2ccccc2)[C@@H](C(=O)O)O1
Agent: Cl
Agent: O=S(=O)(O)O
Agent: [BH4-]
Solvent: CCO
Solvent: O
Product: O=C1N[C@@H](Cc2ccccc2)[C@@H](CO)O1
Reaction time: 3 h

Procedure:
22.1 g (100 mmol) of (4S,5S)-4-benzyl-oxazolidin-2-one-5-carboxylic acid were dissolved in 120 ml of ethanol. 1.2 ml of concentrated sulphuric acid(11 mmol) were added and the mixture refluxed for 2 hours. 90 ml of ethanolwere then removed by distillation. This solution was then added dropwise within 30 minutes to a suspension of 5.3 g (140 mmol) of NaBH4 in 40 ml of ethanol. Once addition was complete, stirring was continued for 3 hours. 100 ml of water were cautiously added to the colourless suspension and a pH value of 7 was established with concentrated HCl. After 2 hours' stirring at room temperature, the temperature was reduced to 0° C. for a further 2 hours. The solid was filtered out and washed with a littleiced water. The product was then dried under a vacuum at 45° C.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH2:16]1[CH2:22][S:19](=[O:21])(=[O:20])[O:18][CH2:17]1>CC(C)=O>[S:19]([CH2:22][CH2:16][CH2:17][N:13]1[CH2:12][CH2:11][N:10]([C:7]2[CH:6]=[CH:5][C:4]([C:1](=[O:3])[CH3:2])=[CH:9][CH:8]=2)[CH2:15][CH2:14]1)([OH:21])(=[O:20])=[O:18]
Reactant: CC(=O)c1ccc(N2CCNCC2)cc1
Reactant: O=S1(=O)CCCO1
Solvent: CC(C)=O
Product: CC(=O)c1ccc(N2CCN(CCCS(=O)(=O)O)CC2)cc1
Temperature: 25 °C

Procedure:
A 4.1 g quantity (20 mmols) of 1-(p-acetylphenyl)piperazine is dissolved in 40 ml of acetone, and a solution of 2.44 g (20 mmols) of 1,3-propanesultone in 10 ml of acetone is added dropwise thereto at room temperature with stirring. After reaction at room temperature with stirring overnight, the yellow crystals precipitated are collected by filtration and then recrystallized from water-acetone.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:14]3[CH:15]=[C:16]([C:18]([O:20][CH3:21])=[O:19])[NH:17][C:13]=3[CH:12]=[CH:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1.Br[CH2:35][CH2:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:14]3[CH:15]=[C:16]([C:18]([O:20][CH3:21])=[O:19])[N:17]([CH2:35][CH2:36][CH2:37][C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[C:13]=3[CH:12]=[CH:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: COC(=O)c1cc2c(-c3cccc(OC)c3)nccc2[nH]1
Reactant: BrCCCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COC(=O)c1cc2c(-c3cccc(OC)c3)nccc2n1CCCc1ccccc1
Temperature: 100 °C
Reaction time: 8 h
Yield: 95.9 %

Procedure:
Methyl 4-(3-methoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (50 mg, 0.177 mmole) and K2CO3 (49.0 mg, 0.354 mmole) were combined in a screw cap vial. To this was added 1,4-dioxane (0.75 mL) and 1-bromo-3-phenylpropane (0.035 mL, 0.230 mmole). The vial was capped then heated to 100° C. After stirring overnight the mixture was cooled to RT and diluted with EtOAc. The mixture was filtered through Celite washing with EtOAc. The filtrate was concentrated. Flash column (Biotage-SNAP-10 g SiO2, 30% EtOAc/hexanes) gave the title compound (68 mg, 96%) as a pale yellow oil. 1H NMR (399 MHz, CDCl3): δ 8.46 (d, J=6.0 Hz, 1 H); 7.58 (d, J=1.0 Hz, 1 H); 7.55-7.50 (m, 2 H); 7.48-7.39 (m, 1 H); 7.32-7.27 (m, 2H); 7.23-7.17 (m, 3 H); 7.09 (dd, J=6.0, 1.0 Hz, 1 H); 7.02 (ddd, J=8.2, 2.7, 1.1 Hz, 1 H); 4.65-4.57 (m, 2 H); 3.91 (m, 6 H); 2.76-2.68 (m, 2 H); 2.21-2.13 (m, 2 H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:8][CH2:9][C:10](Br)=[O:11]>CN(C=O)C.O1CCOCC1>[Br:8][CH2:9][C:10]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:11]
Reactant: O=C(Br)CBr
Reactant: Nc1ccccc1
Solvent: C1COCCO1
Solvent: CN(C)C=O
Product: O=C(CBr)Nc1ccccc1
Temperature: 25 °C
Reaction time: 7 h
Yield: 67.4 %

Procedure:
Aniline (19.4 g, 0.043 mol) was dissolved in the mixture of DMF (25 mL) and dioxane (25 mL). The solution was cooled to +5° C. and bromoacetyl bromide (3.8 mL=8.7 g, 100 mol %) was added dropwise over 30 min. The reaction mixture was warmed to room temperature and stirred for 7 h. The mixture was poured into ice-water, and the white crystalline compound which precipitated was filtered, washed several times with cold water, and then air dried for 24 h, giving 6.2 g (68%) of title compound: 1H NMR (CDCl3) δ8.20 (bs, 1H), 7.54 (dd, J=8.8, J=1.2, 2H), 7.37 (t, J=7.2, 1H), 7.18 (t, J=8, 1H), 4.03 (s, 2H): 13C NMR (CDCl3) δ163.35, 136.88, 129.21, 129.18, 129.11, 125.21, 120.03, 29.47; MS (El, m/z) 213 (M+).
Reaction SMILES: [C:1]([Si:3]([CH3:6])([CH3:5])[CH3:4])#[CH:2].[N+:7]([C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[CH:12]=[O:13])([O-:9])=[O:8]>CCCCCC.O1CCCC1>[N+:7]([C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=1[CH:12]([OH:13])[C:2]#[C:1][Si:3]([CH3:6])([CH3:5])[CH3:4])([O-:9])=[O:8]
Reactant: C#C[Si](C)(C)C
Reactant: O=Cc1ccccc1[N+](=O)[O-]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C[Si](C)(C)C#CC(O)c1ccccc1[N+](=O)[O-]
Temperature: -76 °C
Reaction time: 0.5 h

Procedure:
Into a round-bottomed flask was placed ethynyltrimethylsilane (4.90 mL), and tetrahydrofuran (THF) and was cooled to −76° C. A solution of 2.0 M n-butullithium in hexane (15.8 mL) was added dropwise. The reaction mixture was stirred at −76° C. for 30 minutes and a solution of o-nitrobenzaldehyde (3.0 g) in anhydrous THF was added. The reaction mixture was stirred at −76° C. for 60 minutes, and quenched with water. The reaction mixture was warmed up to room temperature and THF was removed under vacuum. The aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and evaporated to dryness. The crude material was purified by chromatography on silica gel giving a yield of 4.3 grams (87%).
Reaction SMILES: C([N:4]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])C=C.ClC1C=CC=[C:44]([C:48](OO)=[O:49])[CH:43]=1.C(OCC)(=O)C.CO>C(Cl)Cl>[CH2:48]([O:49][N:4]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH:44]=[CH2:43]
Reactant: C=CCN(CCCCCCCCCCCCCCCCCC)CCCCCCCCCCCCCCCCCC
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CCOC(C)=O
Solvent: CO
Solvent: ClCCl
Product: C=CCON(CCCCCCCCCCCCCCCCCC)CCCCCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 5 h
Yield: 63.4 %

Procedure:
Into a cooled solution of 5.0 g (9 mmol) of N-allyl-N,N-dioctadecylamine in 50 ml of methylene chloride at 0° C. under a nitrogen atmosphere is added dropwise with stirring a solution of 1.54 g (9 mmol) of 85% active m-chloroperbenzoic acid in 50 ml of methylene chloride. After the addition is complete (approximately 15 minutes), the resultant solution is allowed to warm to ambient temperature (about 22°-24° C.). The reaction is complete after about 5 hours when TLC analysis (silica gel, 19:1 v/v ethyl acetate:methanol)indicates the starting material has completely reacted. The reaction mixture is transferred to a separatory funnel and washed sequentially with three 50 ml portions of 10% aqueous sodium hydroxide solution and then with 100 ml of distilled water. The organic layer is dried over anhydrous sodium sulfate and heated under reflux at approximately 40° C. for two hours. The resultant solution is concentrated in vacuo and the residue is purified by flash chromatography (silica gel, 94:6 v/v hexane:ethyl acetate eluent) to give 3.3 g (64% yield) of the title compound as a white solid melting at 62°-65° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=S)[NH:11][C@H:12]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:16][CH:15]=1>CN(C=O)C.Cl[Hg]Cl>[CH2:27]([O:26][C:24](=[O:25])[CH2:23][CH2:22][CH2:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][C@@H:12]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[NH:11][C:10]2[NH:9][C:3]3[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=3[N:1]=2)=[CH:15][CH:16]=1)[CH3:28]
Reactant: CCOC(=O)CCCOc1ccc(C[C@H](NC(=S)Nc2ccc(C)cc2N)C(=O)OC(C)(C)C)cc1
Agent: Cl[Hg]Cl
Solvent: CN(C)C=O
Product: CCOC(=O)CCCOc1ccc(C[C@H](Nc2nc3cc(C)ccc3[nH]2)C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 87.6 %

Procedure:
70 mg of HgCl2 is added to the amino thiourea 4-3b (55 mg) in 5 ml of DMF and 0.5 ml of TEA, followed by agitating for 2 hours at ambient temperature, evaporating under reduced pressure and taking up in a water/NaHCO3/AcOEt mixture, decanting, drying the organic phase over Na2SO4 and evaporating to dryness under reduced pressure. 45 mg of crude product 4-4b is obtained.