Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([S:15][CH:16]([CH2:21][CH2:22][CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:17][C:18](O)=[O:19])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.C[Si](C)(C)[O:39][NH2:40]>CN(C)C=O.ClCCl>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([S:15][CH:16]([CH2:21][CH2:22][CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:17][C:18]([NH:40][OH:39])=[O:19])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C[Si](C)(C)ON
Reactant: COc1ccc(SC(CCCCc2ccccc2)CC(=O)O)cc1OC1CCCC1
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1ccc(SC(CCCCc2ccccc2)CC(=O)NO)cc1OC1CCCC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A stirred solution of (±)-3-(3-cyclopentyloxy-4-methoxyphenyl)sulfanyl-7-phenylheptanoic acid (0.40 g, Example 4) in a mixture of dimethylformamide (0.07 ml) and dichloromethane (20 ml) was treated dropwise with a solution of oxalyl chloride in dichloromethane (1.17 ml, 2.0 M). After stirring at room temperature for a further 30 minutes the mixture was treated dropwise with O-(trimethylsilyl)hydroxylamine (0.57 ml). The resulting white suspension was stirred for 10 minutes then partitioned between hydrochloric acid (50 ml, 1N) and ethyl acetate (50 ml). The aqueous layer was extracted twice with ethyl acetate (50 ml). The combined organic phases were washed with water (50 ml), then with brine (50 ml), then dried over magnesium sulphate and then evaporated to give the title compound (0.26 g) as a white foam. NMR (CDCl3): δ1.60 (m,8H), 1.86 (m,6H), 2.35 (br d,2H), 2.60 (br t,2H), 3.30 (m,1H), 3.80 (s,3H), 3.73 (m,1H), 6.76 (d,1H), 6.95 (d,2H), 7.10-7.30 (m,5H). Mass spectrum (FAB): m/z 444 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:35])=[C:6]([NH:8][C:9]([C:11]2[N:12]=[CH:13][NH:14][C:15]=2[C:16]([NH:18][C:19]2[NH:23][C:22]3[C:24]([O:28][CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)=[CH:25][CH:26]=[CH:27][C:21]=3[N:20]=2)=[O:17])=[O:10])[CH:7]=1.[C:36](#N)C.C=O.C([BH3-])#N.[Na+]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:35])=[C:6]([NH:8][C:9]([C:11]2[N:12]=[CH:13][NH:14][C:15]=2[C:16]([NH:18][C:19]2[NH:23][C:22]3[C:24]([O:28][CH:29]4[CH2:34][CH2:33][N:32]([CH3:36])[CH2:31][CH2:30]4)=[CH:25][CH:26]=[CH:27][C:21]=3[N:20]=2)=[O:17])=[O:10])[CH:7]=1
Reactant: Cc1ccc(Br)cc1NC(=O)c1nc[nH]c1C(=O)Nc1nc2cccc(OC3CCNCC3)c2[nH]1
Reactant: CC#N
Agent: C=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1ccc(Br)cc1NC(=O)c1nc[nH]c1C(=O)Nc1nc2cccc(OC3CCN(C)CC3)c2[nH]1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
N4-(5-Bromo-2-methylphenyl)-N5-(7-(piperidin-4-yloxy)-1H-benzo[d]imidazol-2-yl)-1H-imidazole-4,5-dicarboxamide (0.1 mmol) was weighted out into a round bottomed flask and acetonitrile (5 mL) was added and the resulting solution was stirred at 25° C. Formaldehyde (1.0 mmol) and sodium cyanoborohydride (0.32 mmol) was added. The reaction mixture was kept neutral by the addition of acetic acid. After 2 hours, the reaction mixture was concentrated under reduced pressure. The crude product was purified via reverse phase HPLC (aqueous ammonium acetate/acetonitrile) to give N4-(5-bromo-2-methylphenyl)-N5-{7-[(1-methylpiperidin-4-yl)oxy]-1H-benzimidazol-2-yl}-1H-imidazole-4,5-dicarboxamide as a white solid. 1H-NMR (400 MHz, DMSO-d6): δ 8.06 (s, 1H), 7.97 (s, 1H), 7.35 (m, 1H), 7.28 (d, 1H), 7.12 (dd, 1H), 6.99 (m, 1H), 6.67 (m, 1H), 4.67 (m, 1H), 2.32 (m, 4H), 2.19 (s, 3H), 1.89 (m, 5H), MS (EI): 553.3 (MH+).
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].[C:5]([O:9][C:10](=[O:13])[CH2:11]Br)([CH3:8])([CH3:7])[CH3:6]>ClCCl>[C:5]([O:9][C:10](=[O:13])[CH2:11][NH:4][CH2:1][CH:2]=[CH2:3])([CH3:8])([CH3:7])[CH3:6]
Reactant: C=CCN
Reactant: CC(C)(C)OC(=O)CBr
Solvent: ClCCl
Product: C=CCNCC(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 3 h
Yield: 100 %

Procedure:
Allylamine (10 mL, 0.13 mol) was cooled to 0° C., and a solution of bromoacetic acid tert-butyl ester (1.0 mL, 6.7 mmol) in dichloromethane (10 mL) was slowly added. After stirring at 0° C. for 3 hours, the reaction mixture was concentrated under reduced pressure. The obtained residue was dissolved in diethyl ether, washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The obtained solution was concentrated under reduced pressure to give the title compound as a yellow liquid (1.15 g, 6.7 mmol, 99%).
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[C:13]2[CH:12]=[C:11]([C:14]3[C:19]([CH3:20])=[CH:18][N:17]=[C:16]([Cl:21])[N:15]=3)[S:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][CH2:31][NH2:32])[CH2:25][CH2:24]1>O1CCOCC1>[ClH:21].[ClH:21].[ClH:21].[CH3:1][NH:2][C:3]([C:5]1[C:13]2[CH:12]=[C:11]([C:14]3[C:19]([CH3:20])=[CH:18][N:17]=[C:16]([NH:32][CH2:31][CH2:30][CH2:29][N:26]4[CH2:25][CH2:24][N:23]([CH3:22])[CH2:28][CH2:27]4)[N:15]=3)[S:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4]
Reactant: CNC(=O)c1cccc2sc(-c3nc(Cl)ncc3C)cc12
Reactant: CN1CCN(CCCN)CC1
Solvent: C1COCCO1
Product: CNC(=O)c1cccc2sc(-c3nc(NCCCN4CCN(C)CC4)ncc3C)cc12
Product: Cl
Temperature: 95 °C

Procedure:
A stirred mixture of 2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid methylamide (400 mg, 1.26 mmol) and 3-(4-methylpiperazin-1-yl)-propylamine (594 mg, 3.78 mmol) in 1,4-dioxane (6 mL) is heated at 95° C. under a nitrogen atmosphere for 60 hours. After concentration and subsequent chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 0-8%, the free base of the title compound is obtained as a solid (325 mg, 59% yield). The free base (300 mg, 0.684 mmol) is dissolved in MeOH (20 mL) and dichloromethane (20 mL) and the solution is bubbled with a small stream of anhydrous HCl gas for 2 minutes. After concentration, the solid is suspended in MeOH (5 mL) and diethyl ether (20 mL), sonicated, filtered and dried at 60° C. under vacuum to give the title compound as a yellow solid (311 mg, 83% yield). ES+(m/z) 439 [M(free base)+H].
Reaction SMILES: Cl.Cl.[CH2:3]([O:5][C:6](=[O:12])[CH2:7][NH:8][CH2:9][CH2:10][NH2:11])[CH3:4].C(N(CC)CC)C.[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[C:23]([N+:31]([O-:33])=[O:32])[CH:22]=1>ClCCl>[CH2:3]([O:5][C:6](=[O:12])[CH2:7][NH:8][CH2:9][CH2:10][NH:11][S:27]([C:24]1[CH:25]=[CH:26][C:21]([CH3:20])=[CH:22][C:23]=1[N+:31]([O-:33])=[O:32])(=[O:28])=[O:29])[CH3:4]
Reactant: Cc1ccc(S(=O)(=O)Cl)c([N+](=O)[O-])c1
Reactant: CCOC(=O)CNCCN
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)CNCCNS(=O)(=O)c1ccc(C)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.7 %

Procedure:
To a solution of N-(2-aminoethyl)-glycine ethyl ester 2HCl (1.10 g, 5.0 mmol), prepared as described by Will (D. W. Will et al., Tetrahedron, 1995, 51, 12069–12802.), in dichloromethane (50 mL) was slowly added triethylamine (2.02 g, 20 mmol) at room temperature. Then 4-methyl-2-nitro-benzenesulfonyl chloride (1.19 g 5.0 mmol) in dichloromethane (10 mL) was added to the reaction mixture at room temperature for 5 min. The resulting reaction mixture was stirred for additional 2 h. at room temperature and washed with water (30 mL). The organic layer was dried over MgSO4 and filtered. The filtrate was evaporated in vacuo to give desired product (1.60 g, 92%) as a solid. 1H-NMR (500 MHz; DMSO-d6) δ 7.87 (d, 1H), 7.81 (s, 1H), 7.66 (d, 1H), 4.06 (q, 2H), 3.24 (s, 2H), 2.91 (t, 2H), 2.57 (t, 2H), 2.44 (s, 3H), 1.17 (t, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:17]=[CH:16][CH:15]=[CH:14][C:3]=1[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH3:13])=[CH:8][N:7]=1.[C:18](OC(=O)C)(=[O:20])C.NC1C=CC=CC=1CCC1C=CC=CN=1>C(O)=O>[CH2:12]([C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][C:3]2[CH:14]=[CH:15][CH:16]=[CH:17][C:2]=2[NH:1][CH:18]=[O:20])=[N:7][CH:8]=1)[CH3:13]
Reactant: CCc1ccc(CCc2ccccc2N)nc1
Reactant: CC(=O)OC(C)=O
Agent: Nc1ccccc1CCc1ccccn1
Solvent: O=CO
Product: CCc1ccc(CCc2ccccc2NC=O)nc1

Procedure:
Reaction of 2-(o-aminophenethyl)-5-ethylpyridine with acetic anhydride and formic acid according to the procedure described in Example 2 (b) for 2-(o-aminophenethyl)pyridine provides the formylated product 5-ethyl-2-(o-formamidophenethyl)pyridine which can be crystallized from isopropyl ether, m.p. 62°-63.5° C. (corr.).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[OH:9].[C:10](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[O:9][CH3:10]
Reactant: O=C([O-])[O-]
Reactant: Cc1ccc(Cl)c(O)c1
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COc1cc(C)ccc1Cl
Temperature: 25 °C
Reaction time: 3 h
Yield: 102.9 %

Procedure:
To a solution of 2-chloro-5-methylphenol (5.00 g) and potassium carbonate (7.27 g) in anhydrous dimethylformamide (30 mL) was added methyl iodide (3.27 mL), and the mixture was stirred for 3 hours at ambient temperature. The mixture was partitioned between water and ethyl acetate. The separated organic layer was washed with water and brine and dried over magnesium sulfate. The resultant was evaporated in vacuo to give 4-chloro-3-methoxytoluene as a colorless oil (5.65 g).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]([I:15])=[CH:13][N:12]=[C:11](Cl)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)([O-])O.[Na+].C(OCC)(=O)C.[F:43][C:44]1[CH:45]=[C:46]([CH:48]=[CH:49][CH:50]=1)[NH2:47]>CN1CCCC1=O>[CH2:1]([O:8][C:9]1[C:14]([I:15])=[CH:13][N:12]=[C:11]([NH:47][C:46]2[CH:48]=[CH:49][CH:50]=[C:44]([F:43])[CH:45]=2)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1cccc(F)c1
Reactant: Clc1ncc(I)c(OCc2ccccc2)n1
Agent: CC1(C)C2CC[C@@]1(CS(=O)(=O)O)C(=O)C2
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: Fc1cccc(Nc2ncc(I)c(OCc3ccccc3)n2)c1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
To a solution of 4-(benzyloxy)-2-chloro-5-iodopyrimidine (J1, 158 mg) in N-methylpyrrolidone (2.5 mL), 3-fluoroaniline (66 μL) and (1S)-(+)-10-camphorsulfonic acid (159 mg) were added at room temperature, and the mixture was stirred at 60° C. for 2 hours, and then stirred at 80° C. for 7 hours. The reaction mixture was cooled to room temperature, and then saturated aqueous sodium hydrogencarbonate and ethyl acetate were added. The organic layer was separated, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 4-(benzyloxy)-N-(3-fluorophenyl)-5-iodopyrimidin-2-amine (J2, 60 mg) as white solid.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[N:3]=1.[NH:22]1[CH:26]=[N:25][C:24]([C:27]2[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=2)=[N:23]1>>[N:30]1[CH:29]=[CH:28][C:27]([C:24]2[N:25]=[CH:26][N:22]([C:2]3[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([C:12]4[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=4)[N:3]=3)[N:23]=2)=[CH:32][CH:31]=1
Reactant: c1cc(-c2nc[nH]n2)ccn1
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(Cl)n2)cc1
Product: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(-n3cnc(-c4ccncc4)n3)n2)cc1

Procedure:
The title compound was prepared from 2-chloro-4-trifluoromethyl-6-(4-trifluoromethylphenyl)-pyrimidine (example A.2) (0.16 g, 0.5 mmol) and 4-(1H-[1,2,4]-triazol-3-yl)-pyridine [CAS-No. 14803-99-7] (0.075 g, 0.51 mmol) according to the general procedure IVa. Obtained as a white solid (0.096 g, 44%). MS (ISP) 437.3 [(M+H)+]; mp 248° C.
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.[F:6][C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:9][C:8]=1[N:20]1[C:28]2[CH2:27][CH2:26][CH2:25][CH2:24][C:23]=2[C:22](=O)[NH:21]1>[OH-].[Na+]>[Cl:3][C:28]1[N:20]([C:8]2[CH:9]=[C:10]([O:14][CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:11]([Cl:13])=[CH:12][C:7]=2[F:6])[N:21]=[C:22]2[C:27]=1[CH2:26][CH2:25][CH2:24][CH2:23]2
Reactant: O=c1[nH]n(-c2cc(OC3CCCC3)c(Cl)cc2F)c2c1CCCC2
Reactant: O=P(Cl)(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Product: Fc1cc(Cl)c(OC2CCCC2)cc1-n1nc2c(c1Cl)CCCC2
Temperature: 160 °C
Reaction time: 0.5 h
Yield: 26.5 %

Procedure:
Phosphorus oxychloride (6.6 g, 43.0 mmol) was added to the resulting 2N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-one (15.0 g, 42.8 mmol), followed by stirring for 30 minutes while heating at 160° C. After cooling the reaction solution, an ice-cooled dilute aqueous solution of sodium hydroxide (50 ml) was added thereto, and the mixture was extracted with methylene chloride (200 ml×4). The extract was washed with a dilute aqueous sodium hydroxide (400 ml) and a saturated aqueous solution of sodium chloride (400 ml), and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (development solvent: ethyl acetate/hexane=1/9-1/5) to obtain 3-chloro-2N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-4,5,6,7-tetrahydro-2H-indazole as a white solid (4.3 g 26.5% yield).
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[NH:7][C:8]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([NH2:15])[C:9]=1[F:16])([CH3:4])([CH3:3])[CH3:2].[CH3:18][CH:19]([S:21](Cl)(=[O:23])=[O:22])[CH3:20].N1C=CC=CC=1>ClCCl>[C:1]([O:5][C:6](=[O:17])[NH:7][C:8]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([NH:15][S:21]([CH:19]([CH3:20])[CH3:18])(=[O:23])=[O:22])[C:9]=1[F:16])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1c(F)ccc(N)c1F
Reactant: CC(C)S(=O)(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)S(=O)(=O)Nc1ccc(F)c(NC(=O)OC(C)(C)C)c1F
Temperature: 50 °C
Reaction time: 2 h
Yield: 65 %

Procedure:
The tert-butyl-3-amino-2,6-difluorophenylcarbamate (100 mg, 0.41 mmol) prepared at Step 3 was added and dissolved into dichloromethane solvent. 2-propane sulfonyl chloride (50 uL, 0.45 mmol) and pyridine (36 uL, 0.045 mmol) were added into the reaction solution and stirred at 50° C. for 2 hours. After the reaction, the reactant was washed with 1N aqueous hydrochloric acid solution and salt water. After extraction with dichloromethane, the organic layer was dried with sulfuric anhydride magnesium and vacuum concentrated, and then refined by means of column chromatography, so that 94 mg of the target compound, tert-butyl-2,6-difluoro-3-(1-methylethylsulfonamido)phenylcarbamate (percentage yield: 65%), was obtained.
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]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C:19]1[N:24]=[CH:23][CH:22]=[CH:21][N:20]=1)=[O:11].Cl[C:26]1[N:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][N:27]=1>>[F:18][C:16]1[CH:15]=[CH:14][C:13]([C:19]2[N:20]=[CH:21][CH:22]=[CH:23][N:24]=2)=[C:12]([C:10]([N:4]2[CH2:5][CH2:6][CH2:7][C@@H:8]([CH3:9])[C@H:3]2[CH2:2][NH:1][C:26]2[N:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][N:27]=2)=[O:11])[CH:17]=1
Reactant: C[C@@H]1CCCN(C(=O)c2cc(F)ccc2-c2ncccn2)[C@@H]1CN
Reactant: FC(F)(F)c1cnc(Cl)nc1
Product: C[C@@H]1CCCN(C(=O)c2cc(F)ccc2-c2ncccn2)[C@@H]1CNc1ncc(C(F)(F)F)cn1

Procedure:
The title compound was prepared following the same general protocol as described for Example A1, using ((2S,3R)-2-(aminomethyl)-3-methylpiperidin-1-yl)(5-fluoro-2-(pyrimidin-2-yl)phenyl)methanone and 2-chloro-5-(trifluoromethyl)pyrimidine. ESI-MS (m/z): 475 [M+1]+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:9])=[C:6]([SH:8])[CH:7]=1.[C:10](OCC)(=O)[C:11]([O:13][CH2:14][CH3:15])=[O:12].O.Cl>CCO>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[S:8][C:6]=2[CH:7]=1
Reactant: Nc1ccc(F)cc1S
Reactant: CCOC(=O)C(=O)OCC
Agent: Cl
Solvent: O
Solvent: CCO
Product: CCOC(=O)c1nc2ccc(F)cc2s1

Procedure:
A solution of 5-fluoro-2-aminobenzenethiol (0.94 g, 6.6 mmol) in diethyl oxalate (1.8 mL, 13 mmol) is heated at reflux for overnight. The solution is poured into a mixture of water (9.8 mL), conc. HCl (3.3 mL), and EtOH (4.6 mL). The material is extracted with CHCl3 (3×100 mL). The combined organic extracts are dried over MgSO4, filtered and concentrated to yield an oil. The material is purified by chromatography (25% hexanes/75% CHCl3) to afford a solid that is recrystallized from petroleum ether (0.16 g, 11%). MS for C10H8NO2SF: m/z 226 (M+H)+.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH:7](I)([CH3:9])[CH3:8].[OH:11][C:12]1[CH:21]=[CH:20][C:15]2[S:16][C:17](=[O:19])[O:18][C:14]=2[CH:13]=1.O>CN(C)C=O>[CH:7]([O:11][C:12]1[CH:21]=[CH:20][C:15]2[S:16][C:17](=[O:19])[O:18][C:14]=2[CH:13]=1)([CH3:9])[CH3:8]
Reactant: CC(C)I
Reactant: O=c1oc2cc(O)ccc2s1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)Oc1ccc2sc(=O)oc2c1
Reaction time: 4 h

Procedure:
Potassium carbonate (829 mg) and isopropyl iodide (300 μL) were added to a solution of 6-hydroxy-1,3-benzoxathiol-2-one (504 mg) in N,N-dimethylformamide (15 mL) to form a reaction solution. This reaction solution was stirred for 4 hours at normal temperature, and then for 8 hours at 40° C. Water was added to the reaction solution, and the reaction solution was extracted with ethyl acetate. The extract was washed with water and saturated brine in that order, and then dried over anhydrous sodium sulfate. The anhydrous sodium sulfate was removed by filtration, and then the solvent was removed by distillation under reduced pressure. The resultant product was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain the target product (300 mg) as a colorless oil.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[C:7](Br)[CH:6]=[C:5]([CH:10]=[O:11])[C:4]=1[OH:12])=[O:2].[CH:13]#[C:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>C(#N)C.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:1]([C:3]1[CH:8]=[C:7]([C:13]#[C:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:6]=[C:5]([CH:10]=[O:11])[C:4]=1[OH:12])=[O:2]
Reactant: O=Cc1cc(Br)cc(C=O)c1O
Reactant: C#CCCCCCCCCCC
Agent: c1ccc([P]([Pd][P](c2ccccc2)(c2ccccc2)c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: CCCCCCCCCCC#Cc1cc(C=O)c(O)c(C=O)c1
Temperature: 80 °C
Reaction time: 12 h
Yield: 45.5 %

Procedure:
2,6-Diformyl-4-bromophenol (2.50 g, 10.9 mmol), 1-dodecyne (2.00 g, 12.0 mmol), Cul (65 mg, 0.33 mmol), and bis(triphenylphosphine)palladium)II)dichloride were suspended in degassed acetonitrile (MeCN) (5 mL) and degassed benzene (1 mL). The yellow suspension was sparged with argon for 30 min and degassed Et3N (1 mL) was added. The resulting brown suspension was sealed in a pressure vial, warmed to 80° C. and held there for 12 h. The mixture was then partitioned between EtOAc and KHSO4 solution. The organic layer was separated, washed with brine, dried MgSO4) and concentrated under reduced pressure. The dark yellow oil was purified by column chromatography on silica gel (25% Et2O in hexanes) to give 1.56 g (46%) of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4](O)=[O:5].Cl.[NH:24]1[CH2:29][CH2:28][C:27]2([C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:31][O:30]2)[CH2:26][CH2:25]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C(=O)C>[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([N:24]1[CH2:29][CH2:28][C:27]2([C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:31][O:30]2)[CH2:26][CH2:25]1)=[O:5]
Reactant: c1ccc2c(c1)COC21CCNCC1
Reactant: O=C(O)c1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CC(=O)N(C)C
Product: O=C(c1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F)N1CCC2(CC1)OCc1ccccc12
Temperature: 25 °C
Reaction time: 5 h
Yield: 52.4 %

Procedure:
A solution of 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (144 mg, 0.48 mmol) and 3H-spiro[isobenzofuran-1,4′-piperidine]hydrochloride (109 mg, 0.48 mmol) in N,N-dimethylacetamide (2 mL) was treated with triethylamine (0.168 mL, 1.21 mmol) and O-Benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (256 mg, 0.68 mmol). The resulting mixture was stirred at ambient temperature for 5 hours, before being filtered and purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 0.1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness and lyophilised to afford the desired compound as a white solid (118 mg, 52.1% yield); 1H NMR (400.132 MHz, DMSO) δ 1.53-1.62 (2H, m), 1.73-1.83 (3H, m), 1.91-1.99 (1H, m), 3.10-3.18 (1H, m), 4.40 (2H, s), 4.54-4.60 (1H, m), 5.03-5.11 (2H, m), 7.26-7.37 (5H, m), 7.45-7.50 (2H, m), 7.83-7.93 (2H, m), 8.02 (1H, d), 8.30 (1H, d), 12.13-12.59 (1H, br s); m/z (LC-MS, ESI+), RT=2.14 (M+H 470.9).
Reaction SMILES: [CH2:1]1[O:14][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].[NH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][NH2:22]>>[CH2:21]([NH:22][CH2:1][CH:2]([OH:14])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][NH:15][CH2:1][CH:2]([OH:14])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCCCCCCCCC1CO1
Reactant: NCCCCCCN
Product: CCCCCCCCCCCC(O)CNCCCCCCNCC(O)CCCCCCCCCCC

Procedure:
Condensation of 1-tridecene oxide and hexamethylenediamine affords N,N'-(1,6-hexylene)-bis[2-hydroxytridecylamine] (I: R= CH3 (CH2)10, R' = H, X= (CH2)6, Z= H).
Reaction SMILES: [C:1]1([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[NH:9][C:8]2=[O:24])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:25][C:26](Br)(CCC)[CH2:27][CH2:28]C.C(=O)([O-])[O-].[K+].[K+].[CH3:40][C:41](=O)[CH2:42][CH3:43]>>[C:1]1([N:7]2[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:9]([CH2:40][CH2:41][CH2:42][CH2:43][CH2:28][CH2:27][CH2:26][Br:25])[C:8]2=[O:24])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=c1[nH]c(-c2ccccc2)c(-c2ccccc2)n1-c1ccccc1
Reactant: CCC(C)=O
Reactant: CCCC(Br)(Br)CCC
Agent: O=C([O-])[O-]
Agent: [K+]
Product: O=c1n(CCCCCCCBr)c(-c2ccccc2)c(-c2ccccc2)n1-c1ccccc1
Yield: 46 %

Procedure:
A mixture of 1,4,5-triphenylimidazol-2-one (15.3g), dibromoheptane (50.6g) and potassium carbonate (13.8g) was heated at reflux temperature in dry butanone (750m1) for.20 hours. The mixture was cooled, filtered and the flitrate evaporated to an oil which was chromatographed on silica gel (hexane/ethyl acetate) to give 1,4,5-triphenyl-3-(7-bromoheptyl)imidazole-2-one (11.1 g, 46%) as an oil.
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[C:9]([O:10][CH3:11])=[C:8]([O:12][CH3:13])[CH:7]=[CH:6][N:5]=1.[OH-].[Na+].[Cl:16][C:17]1[CH:26]=[CH:25][C:20]2[NH:21][C:22]([SH:24])=[N:23][C:19]=2[CH:18]=1>CO.O>[Cl:16][C:17]1[CH:26]=[CH:25][C:20]2[NH:21][C:22]([S:24][CH2:3][C:4]3[C:9]([O:10][CH3:11])=[C:8]([O:12][CH3:13])[CH:7]=[CH:6][N:5]=3)=[N:23][C:19]=2[CH:18]=1
Reactant: Sc1nc2cc(Cl)ccc2[nH]1
Reactant: COc1ccnc(CCl)c1OC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1ccnc(CSc2nc3cc(Cl)ccc3[nH]2)c1OC

Procedure:
2-chloromethyl-3,4-dimethoxypyridine hydrochloride (896 mg, 0.004 mol) was dissolved in 25 ml MeOH and treated with NaOH (390 mg, 0.008 mol) dissolved in 1.5 ml H2O. 5-chloro-2-mercapto-1H-benzimidazole (812 mg, 0.0044 mol) was added and the resulting mixture allowed to react for 2h at room temperature. The solvent was evaporated and the residue partitioned between 50 ml 2.5 % NaOH and 75 ml CH2Cl2. The aqueous layer was separated and extracted twice with 25 ml CH2Cl2. The organic layers were combined, washed with 25 ml H2O, dried over MgSO4 and the solvent was evaporated.