Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C@@H:8]([CH2:12][CH2:13][C@H:14]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:15]([NH:17][C@H:18]1[CH2:24][CH2:23][S:22][C@H:21]2[CH2:25][CH2:26][CH2:27][C@@H:28]([C:29]([O:31][CH3:32])=[O:30])[N:20]2[C:19]1=[O:33])=[O:16])[C:9](O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:41][CH:42]1[C:48]([CH3:50])([CH3:49])[CH:47]=[CH:46][CH2:45][N:44]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C:43]1=[O:57]>>[CH2:34]([C@@H:14]([CH2:13][CH2:12][C@H:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:9]([NH:41][C@H:42]1[C:48]([CH3:50])([CH3:49])[CH:47]=[CH:46][CH2:45][N:44]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C:43]1=[O:57])=[O:10])[C:15]([NH:17][C@H:18]1[CH2:24][CH2:23][S:22][C@H:21]2[CH2:25][CH2:26][CH2:27][C@@H:28]([C:29]([O:31][CH3:32])=[O:30])[N:20]2[C:19]1=[O:33])=[O:16])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: COC(=O)[C@@H]1CCC[C@@H]2SCC[C@H](NC(=O)[C@H](CC[C@H](Cc3ccccc3)C(=O)O)Cc3ccccc3)C(=O)N21
Reactant: CC1(C)C=CCN(c2ccccc2)C(=O)C1N
Product: COC(=O)[C@@H]1CCC[C@@H]2SCC[C@H](NC(=O)[C@H](CC[C@H](Cc3ccccc3)C(=O)N[C@@H]3C(=O)N(c4ccccc4)CC=CC3(C)C)Cc3ccccc3)C(=O)N21

Procedure:
(4S,7S,10aS)-Methyl 4-((2R,5R)-2,5-dibenzyl-6-((S,Z)-4,4-dimethyl-2-oxo-1-phenyl-2,3,4,7-tetrahydro-1H-azepin-3-ylamino)-6-oxohexanamido)-5-oxooctahydro-2H-pyrido[2,1-b][1,3]thiazepine-7-carboxylate was synthesized as described in General Procedure H using Intermediate 23 (10 mg, 0.018 mmol) and Intermediate 33 (4.1 mg, 0.018 mmol) to give a white solid (4.0 mg, 27% yield). Anal. Calcd. for C45H54N4O6S m/z 778.4. found: 779.4 (M+H)+; 1H NMR (500 MHz, CD3OD) δ ppm 8.00-8.08 (m, 1H), 7.31 (t, J=7.70 Hz, 2H), 7.27-7.09 (m, 11H), 6.98 (d, J=7.70 Hz, 2H), 5.77 (ddd, J=11.41, 8.11, 3.57 Hz, 1H), 5.63-5.49 (m, 2H), 5.38 (d, J=9.35 Hz, 1H), 5.04-4.97 (m, 1H), 4.96-4.90 (m, 1H), 3.75 (dd, J=17.60, 8.25 Hz, 1H), 3.59 (s, 3H), 3.03-2.88 (m, 2H), 2.84-2.65 (m, 5H), 2.62-2.53 (m, 1H), 2.34 (d, J=13.75 Hz, 1H), 2.16-2.01 (m, 1H), 1.96 (d, J=10.45 Hz, 1H), 1.89-1.79 (m, 2H), 1.76-1.47 (m, 6H), 1.41-1.30 (m, 1H), 0.89-0.80 (s, 3H), 0.54-0.46 (s, 3H).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([C:14]4[O:18][N:17]=[C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH3:22])[CH:15]=4)=[N:11][C:10]=3[CH:31]=2)[CH2:3][CH2:2]1.[CH2:32]([Li])CCC.IC.Cl>C1COCC1.CCCCCC>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([C:14]4[O:18][N:17]=[C:16]([O:19][CH2:20][C@@H:21]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:29])[CH3:28])[CH3:22])[C:15]=4[CH3:32])=[N:11][C:10]=3[CH:31]=2)[CH2:2][CH2:3]1
Reactant: [Li]CCCC
Reactant: C[C@@H](COc1cc(-c2nc3cc(OCC4CC4)ccc3o2)on1)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CI
Product: Cc1c(OC[C@H](C)NC(=O)OC(C)(C)C)noc1-c1nc2cc(OCC3CC3)ccc2o1
Temperature: -78 °C
Reaction time: 0.33 h

Procedure:
Under an argon atmosphere, to a solution of tert-butyl [(1S)-2-({5-[5-(cyclopropylmethoxy)-1,3-benzoxazol-2-yl]isoxazol-3-yl}oxy)-1-methylethyl]carbamate (644 mg) in THF (15 mL) was added dropwise a hexane solution (1.6 M, 2.156 mL) of n-butyllithium at −78° C., and the mixture was stirred at −78° C. for 20 min. To the reaction mixture was added iodomethane (0.140 mL), and the mixture was stirred at −78° C. for 15 min, and then at 0° C. for 1 hr. The reaction mixture was neutralized with 1M hydrochloric acid, and extracted with ethyl acetate. The combined organic layer 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 (hexane/ethyl acetate) to give the title compound (46.0 mg).
Reaction SMILES: [C:1]([C:4]1[CH:22]=[CH:21][C:7]([C:8]([NH:10][C:11]2[CH:19]=[C:18]([NH2:20])[CH:17]=[CH:16][C:12]=2[C:13]([OH:15])=[O:14])=[O:9])=[CH:6][CH:5]=1)([OH:3])=[O:2].[C:23](Cl)(=[O:26])[CH2:24][CH3:25]>C(O)(C)C>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:10][C:11]2[CH:19]=[C:18]([NH:20][C:23](=[O:26])[CH2:24][CH3:25])[CH:17]=[CH:16][C:12]=2[C:13]([OH:15])=[O:14])=[O:9])=[CH:21][CH:22]=1)([OH:3])=[O:2]
Reactant: CCC(=O)Cl
Reactant: Nc1ccc(C(=O)O)c(NC(=O)c2ccc(C(=O)O)cc2)c1
Solvent: CC(C)O
Product: CCC(=O)Nc1ccc(C(=O)O)c(NC(=O)c2ccc(C(=O)O)cc2)c1
Yield: 62 %

Procedure:
The procedure of Example 4 was repeated to react 2-(4-carboxybenzamido)-4-aminobenzoic acid with propionyl chloride, and the reaction product was treated as in Example 4 except that isopropyl alcohol was used as a solvent for recrystallization. The product obtained was a 62% yield of 2-(4-carboxybenzamido)-4-propionamidobenzoic acid having a melting point in the range of from 284° to 286° C. (decompose).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[C:4]([O:12][C:13]2[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=2)[CH:3]=1.CS(O)(=O)=O>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[CH2:8][C:9](=[O:11])[C:14]3[C:15]([O:21][CH3:22])=[CH:16][C:17]([O:19][CH3:20])=[CH:18][C:13]=3[O:12][C:4]=2[CH:3]=1
Reactant: COc1cc(OC)cc(Oc2cc(Br)ccc2CC(=O)O)c1
Agent: CS(=O)(=O)O
Product: COc1cc(OC)c2c(c1)Oc1cc(Br)ccc1CC2=O
Temperature: 40 °C
Reaction time: 72 h
Yield: 65.9 %

Procedure:
To 27.3 g (F.W. 367.195, 74.3 mmol) of carboxylic acid (26) was added 140 mL of methanesulfonic acid to dissolve carboxylic acid (26). This solution was stirred at 40° C. for three days. To the resulting reaction solution was added 300 mL of ice water to deposit a cyclized compound. The cyclized compound was separated by filtration and extracted with ethyl acetate and treated according to the conventional method to obtain a crude product. This crude product was purified by silica gel column chromatography (developing solvent; ethyl acetate:hexane=1:2) and recrystallized from hexane-ethyl acetate to obtain 17.1 g (66%) of cyclized compound (27).
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][C:6]=1[C:7]([OH:9])=O)([CH3:3])[CH3:2].[N+:18]([C:21]1[S:25][C:24]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[N:23][CH:22]=1)([O-:20])=[O:19]>>[CH:1]([O:4][C:5]1[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][C:6]=1[C:7]([N:29]1[CH2:30][CH2:31][N:26]([C:24]2[S:25][C:21]([N+:18]([O-:20])=[O:19])=[CH:22][N:23]=2)[CH2:27][CH2:28]1)=[O:9])([CH3:2])[CH3:3]
Reactant: O=[N+]([O-])c1cnc(N2CCNCC2)s1
Reactant: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)O
Product: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CCN(c2ncc([N+](=O)[O-])s2)CC1
Yield: 67 %

Procedure:
Prepared in analogy to example 1 (b) from 2-isopropoxy-5-methanesulfonyl-benzoic acid (Example A1) and 1-(5-nitro-thiazol-2-yl)-piperazine. The crude material was purified by chromatography (SiO2, ethyl acetate/heptane) followed by trituration in ether to yield the title compound as a yellow crystalline solid (yield 67%). MS (m/e): 455.4 (M+H+, 100%), 472.0 (M+NH4+, 100%).
Reaction SMILES: [CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([CH2:18][NH2:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10]1.C(O)C.I.CS[C:26]([C:28]1[S:29][CH:30]=[CH:31][CH:32]=1)=[NH:27]>C(OCC)C>[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[CH2:7][CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([CH2:18][NH:19][C:26]([C:28]3[S:29][CH:30]=[CH:31][CH:32]=3)=[NH:27])=[CH:15][CH:16]=2)[CH:11]=[CH:10]1
Reactant: CSC(=N)c1cccs1
Reactant: CN1CCCC1CCn1ccc2cc(CN)ccc21
Agent: I
Solvent: CCO
Solvent: CCOCC
Product: CN1CCCC1CCn1ccc2cc(CNC(=N)c3cccs3)ccc21
Temperature: 25 °C
Reaction time: 96 h
Yield: 56.6 %

Procedure:
Compound 36 (124 mg, 0.482 mmol) and anhydrous ethanol (10 mL) were charged to a dry argon purged flask fitted with magnetic stirbar. Thiophene-2-carboximidothioic acid methyl ester hydroiodide (178.5 mg, 0.626 mmol) is added to the flask and the reaction was stirred under argon at ambient temperature for 96 hours. The solution was diluted with diethyl ether (50 mL) resulting in the formation of an off-white precipitate which was collected on a sintered glass funnel and washed with ether. The solid was partitioned between H2O and ethyl acetate and 3M sodium hydroxide solution added to adjust pH to 9. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered, concentrated and the residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 1:9) to afford a pale yellow residue 37 (100 mg, 56.6%); 1H NMR (DMSO-d6) δ 7.60 (d, 1H, J=3.8 Hz), 7.51 (m, 2H), 7.39-7.34 (2×m, 2H), 7.16-7.13 (m, 1H), 7.06 (dd, 1H, J=3.8, 5.1 Hz), 6.86-6.54 (brs, 2H), 6.37 (d, 1H, J=3.0 Hz), 4.38 (s, 2H), 4.16 (t, 2H, J=7.3 Hz), 2.94-2.87 (m, 1H), 2.16 (s, 3H), 2.11-1.92 (2×m, 3H), 1.89-1.80 (m, 1H), 1.69-1.55 (m, 3H), 1.48-1.36 (m, 1H); ESI-MS (m/z, %): 367 (M+1, 100%).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[NH:11]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:14](=O)[C:12]1=[O:13].Cl>C(O)(=O)C>[CH:18]1[CH:19]=[CH:20][C:21]2[NH:11][C:12](=[O:13])/[C:14](=[C:3]3\[C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:9]=4[NH:1][C:2]\3=[O:10])/[C:16]=2[CH:17]=1
Reactant: O=C1Nc2ccccc2C1=O
Reactant: O=C1Cc2ccccc2N1
Agent: Cl
Solvent: CC(=O)O
Product: O=C1Nc2ccccc2/C1=C1\C(=O)Nc2ccccc21
Yield: 84 %

Procedure:
Isoindigo was synthesized by reaction of oxindole with isatin in acetic acid with addition of hydrochloric acid (Wahl A., Bayard P., Comptes Rendues Hebdomadaires des Seances de L'Academie des Sciences, 148, (1909), 716-719).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]3[NH:25][C:24](=[O:26])[O:23][C:22]([CH:33]4[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]4)([CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)[C:21]=3[CH:39]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[OH:40]O>>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]([S:11]([CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]3[NH:25][C:24](=[O:26])[O:23][C:22]([CH:33]4[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]4)([CH:27]4[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]4)[C:21]=3[CH:39]=2)=[O:40])=[CH:9][CH:10]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1ccc(SCCCCOc2ccc3c(c2)C(C2CCCCC2)(C2CCCCC2)OC(=O)N3)cc1
Reactant: OO
Product: CC(=O)Nc1ccc(S(=O)CCCCOc2ccc3c(c2)C(C2CCCCC2)(C2CCCCC2)OC(=O)N3)cc1

Procedure:
Prepared analogously to Example 2 from 6-[4-(4-acetamido-phenylmercapto)-butoxy]-4,4-dicyclohexyl-4H-3,1-benzoxazin-2-one and hydrogen peroxide.
Reaction SMILES: [CH2:1]([OH:12])[C@H:2]1[O:8][C:6](=[O:7])[C@H:5]([OH:9])[C@@H:4]([OH:10])[C@@H:3]1[OH:11].[CH3:13][NH2:14]>C(O)(C)C.CO>[CH3:13][NH:14][C:6]([C@@H:5]([C@H:4]([C@@H:3]([C@@H:2]([CH2:1][OH:12])[OH:8])[OH:11])[OH:10])[OH:9])=[O:7]
Reactant: O=C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reactant: CN
Solvent: CC(C)O
Solvent: CO
Product: CNC(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
A suspension of 50 g gluconolactone in 500 ml of isopropanol/methanol (4/1) was treated with 23.8 ml of a 40% N-methylamine solution for 30 minutes. The N-methylgluconamide obtained in quantitative yields, was treated at 60° C. with 69 ml acetic anhydride and 35 ml acetic acid in the presence of 1% concentrated sulphuric acid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:10][C:9]=1[NH2:22])([CH3:4])([CH3:3])[CH3:2].C([O:28][C:29](=O)[CH2:30][C:31](=[O:44])[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]2[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=2)[CH:33]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:23])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[CH:10][C:9]=1[NH:22][C:29](=[O:28])[CH2:30][C:31](=[O:44])[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]2[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=2)[CH:33]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1ccc(C#Cc2ccccc2)cc1N
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-c2cccnc2)c1
Product: CC(C)(C)OC(=O)Nc1ccc(C#Cc2ccccc2)cc1NC(=O)CC(=O)c1cccc(-c2cccnc2)c1

Procedure:
The title compound was prepared from (2-amino-4-phenylethynyl-phenyl)-carbamic acid tert-butyl ester {CAS-No. [335255-26-0]} (231 mg, 0.75 mmol) and 3-oxo-3-(3-pyridin-3-yl-phenyl)-propionic acid tert-butyl ester (Example K1) (223 mg, 0.75 mmol) according to the general procedure M. Obtained as a yellow foam (322 mg, 81%).
Reaction SMILES: [OH-].[Na+].[C:3]([C:7]1[N:11]([CH2:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:10]2[CH:19]=[CH:20][C:21]([S:23]([N:26]3[CH2:31][CH2:30][CH2:29][CH:28]([C:32]([O:34]CC)=[O:33])[CH2:27]3)(=[O:25])=[O:24])=[CH:22][C:9]=2[N:8]=1)([CH3:6])([CH3:5])[CH3:4]>CO.O.O>[C:3]([C:7]1[N:11]([CH2:12][CH:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)[C:10]2[CH:19]=[CH:20][C:21]([S:23]([N:26]3[CH2:31][CH2:30][CH2:29][CH:28]([C:32]([OH:34])=[O:33])[CH2:27]3)(=[O:25])=[O:24])=[CH:22][C:9]=2[N:8]=1)([CH3:6])([CH3:4])[CH3:5]
Reactant: CCOC(=O)C1CCCN(S(=O)(=O)c2ccc3c(c2)nc(C(C)(C)C)n3CC2CCOCC2)C1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)(C)c1nc2cc(S(=O)(=O)N3CCCC(C(=O)O)C3)ccc2n1CC1CCOCC1
Reaction time: 8 h

Procedure:
NaOH (0.75 mL, 2M, 1.5 mmol) was added to a solution of ethyl 1-{[2-tert-butyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]sulfonyl}piperidine-3-carboxylate (158 mg, 0.36 mmol) in 10 mL of MeOH—H2O (1:1) at ambient temperature. The reaction mixture was stirred overnight and diluted with water (40 mL). The solvent was concentrated to 40 mL. The resulting solution was neutralized with HCl solution and the product was extracted with EtOAc and dried over anhydrous Na2SO4. The solvent was concentrated to provide the title compound as white solid. Yield: 108 mg (72%); MS (ESI) (M+H)+=464.0.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][CH2:7][CH2:8][NH:9][C:10]([C:12]2[N:13]=[N:14][C:15](Cl)=[CH:16][CH:17]=2)=[O:11])=[CH:4][CH:3]=1.[N:21]1([C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[C:35]([F:38])([F:37])[F:36])=[O:28])[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>>[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][CH2:7][CH2:8][NH:9][C:10]([C:12]2[N:13]=[N:14][C:15]([N:24]3[CH2:25][CH2:26][N:21]([C:27](=[O:28])[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[C:35]([F:38])([F:36])[F:37])[CH2:22][CH2:23]3)=[CH:16][CH:17]=2)=[O:11])=[CH:4][CH:3]=1
Reactant: O=C(c1ccccc1C(F)(F)F)N1CCNCC1
Reactant: O=C(NCCOc1ccc(Cl)cc1)c1ccc(Cl)nn1
Product: O=C(NCCOc1ccc(Cl)cc1)c1ccc(N2CCN(C(=O)c3ccccc3C(F)(F)F)CC2)nn1

Procedure:
Following the procedure of Example 15, making variations only as required to use 6-chloropyridazine-3-carboxylic acid [2-(4-chlorophenoxy)ethyl]amide in place of 6-chloropyridazine-3-carboxylic acid (2-cyclopropyl-2-hydroxyethyl)amide to react with piperazin-1-yl-(2-trifluoromethylphenyl)methanone, the title compound was obtained as a white solid (13% yield). 1H NMR (400 MHz, CDCl3) δ 8.27, 8.05, 7.74, 7.64, 7.57, 7.37, 7.25-7.20, 7.00, 6.85-6.82, 4.02-3.32.
Reaction SMILES: C([C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1)CCC.C(O[C:16](=[O:18])[CH3:17])(=O)C>O>[CH3:11][CH2:5][CH2:6][CH2:7][CH2:17][C:16]([NH:9][C:8]1[CH:7]=[CH:6][CH:5]=[CH:11][CH:10]=1)=[O:18]
Reactant: CC(=O)OC(C)=O
Reactant: CCCCc1ccc(N)cc1
Solvent: O
Product: CCCCCC(=O)Nc1ccccc1
Temperature: 85 °C

Procedure:
One hundred grams of I, 4-n-butylaniline, were stirred with 500 grams H2O and 410 grams acetic anhydride added all at once. The temperature rose spontaneously to 45° C. and was raised briefly to 85° C, to bring all the solids into solution. Slow cooling, filtration, and overnight air drying gave 117.4 grams (92%) white plates of II, 4-butylacetanilide, mp 104°-105° C. (lit.1, mp 107° C). This 117.4 grams II were stirred with 486 grams acetic anhydride and 284 ml. 71% HNO3 added at such a rate that, after a brief induction period and with ice cooling, the temperature was kept at 30°-35° C. The reaction mixture was stirred 30 minutes at 5° C, then 300 grams ice, followed by 600 ml. H2O were added and the yellow solid filtered, washed copiously with H2O, and air dried to give 129.9 grams (90%) bright yellow III, 4-butyl-2-nitroacetanilide, mp 71°-73° C (lit.1, mp 76° C).
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([N+:9]([O-])=O)[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[C:4]([C:19](=[O:21])[CH3:20])[CH:3]=1.[H][H]>CO.[Pt]>[NH2:9][C:6]1[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[C:4]([C:19](=[O:21])[CH3:20])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH3:8]
Reactant: CC(=O)c1cc(Cl)c(C)c([N+](=O)[O-])c1-c1cccc(F)c1
Reactant: [H][H]
Agent: [Pt]
Solvent: CO
Product: CC(=O)c1cc(Cl)c(C)c(N)c1-c1cccc(F)c1
Yield: 102.9 %

Procedure:
A mixture of 1-(4-chloro-3′-fluoro-5-methyl-6-nitrobiphenyl-2-yl)ethanone (4.4 g, 14 mmol) in methanol (80 mL) was hydrogenated in the presence of 5% Pt/C (443 mg) under balloon pressure of hydrogen overnight. The catalyst was filtered and the filtrate was concentrated under reduced pressure to give the desired product (4.0 g, 100%). LCMS calculated for C15H14ClFNO (M+H)+: m/z=278.1. found: 278.1.
Reaction SMILES: [C:1]1([O:7][C:8]([N:10]2[CH2:20][CH2:19][C:13]3[N:14]=[N:15][C:16](Cl)=[CH:17][C:12]=3[CH2:11]2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.[NH2:22][NH2:23]>>[C:1]1([O:7][C:8]([N:10]2[CH2:20][CH2:19][C:13]3[N:14]=[N:15][C:16]([NH:22][NH2:23])=[CH:17][C:12]=3[CH2:11]2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NN
Reactant: O=C(Oc1ccccc1)N1CCc2nnc(Cl)cc2C1
Solvent: O
Product: NNc1cc2c(nn1)CCN(C(=O)Oc1ccccc1)C2

Procedure:
A solution of 20.3 g of crude oily 3-chloro-5,6,7,8-tetrahydro-6-pyrido[4,3-c]pyridazinecarboxylic acid phenyl ester in 100 cc of hydrazine hydrate is stirred in an oil bath of 100° for 11/2 hours. The reaction solution is concentrated in a vacuum and the residue is divided between 225 cc of chloroform and 25 c of water. The crude title compound is obtained as semicrystalline residue upon concentrating the organic phase in a vacuum.
Reaction SMILES: C[SiH:2]([CH2:13]CCCCCCCCC)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH2:23]=[CH:24][CH2:25]CCCCCCC>C1C=CC=CC=1.[C-]#[O+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Rh]>[CH3:13][SiH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:23][CH2:24][CH3:25]
Reactant: CCCCCCCCCC[SiH](C)CCCCCCCCCC
Reactant: C=CCCCCCCCC
Agent: [Rh]
Agent: [C-]#[O+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Product: CCCCCCCCCCCCC[SiH2]C
Yield: 85 %

Procedure:
A mixture of 1.53 grams of methyldidecylsilane, and 0.70 gram of 1-decene in 5 milliliters of benzene was reacted for 25 hours at 50° C. in the presence of 0.005 gram hydridocarbonyltris(triphenylphosphine)rhodium(I). Chromatographic analysis showed that an 85 percent yield of methyltridecylsilane was formed at a 65 percent silane conversion.
Reaction SMILES: [C:1]([O:4][CH2:5][CH2:6][O:7][C:8]1[CH:12]=[C:11]([NH:13][S:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[N:10]([CH3:27])[N:9]=1)(=[O:3])[CH3:2].[I:28]N1C(=O)CCC1=O.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>O1CCCC1.C(OCC)(=O)C.O.[Cl-].[Na+].O>[C:1]([O:4][CH2:5][CH2:6][O:7][C:8]1[C:12]([I:28])=[C:11]([NH:13][S:14]([C:17]2[CH:18]=[CH:19][C:20]([C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:21][CH:22]=2)(=[O:15])=[O:16])[N:10]([CH3:27])[N:9]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OCCOc1cc(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)n(C)n1
Reactant: O=C1CCC(=O)N1I
Agent: O=S([O-])S(=O)(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(=O)OCCOc1nn(C)c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)c1I
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To 2-{[5-({[4-(tert-butyl)phenyl]sulfonyl}amino)-1-methyl-1H-pyrazol-3-yl)oxy}ethyl acetate (Preparation 8) (1.15 g) in solution in tetrahydrofuran (200 ml) was added portionwise N-iodosuccinimide (18 g), at room temperature. The reaction mixture was stirred at room temperature for 2 hours. The reaction was then diluted with ethyl acetate (150 ml), water (50 ml) and brine (50 ml). A 1M solution of sodium metabisulphite (100 ml) was added and the organic layer separated. The organics were washed successively with a diluted solution of sodium metabisulphite (100 ml) and then brine (50 ml). The solution was dried on magnesium sulfate, filtered and concentrated under reduced pressure to yield the desired product as an off pink solid (33.6 g)
Reaction SMILES: C(O)(=O)C.CO[C:7](=[O:36])[CH2:8][CH2:9][NH:10][C:11](=[O:35])[C@@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17](=[O:34])[C@H:18]([CH2:28][C:29]1[N:33]=[CH:32][NH:31][CH:30]=1)[NH:19][C:20](=[O:27])[C@@H:21]1[CH2:25][CH2:24][C:23](=[O:26])[NH:22]1.[NH3:37]>CO>[NH:22]1[C:23](=[O:26])[CH2:24][CH2:25][C@H:21]1[C:20]([NH:19][C@H:18]([C:17]([N:13]1[CH2:14][CH2:15][CH2:16][C@H:12]1[C:11]([NH:10][CH2:9][CH2:8][C:7]([NH2:37])=[O:36])=[O:35])=[O:34])[CH2:28][C:29]1[N:33]=[CH:32][NH:31][CH:30]=1)=[O:27]
Reactant: N
Reactant: COC(=O)CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1
Solvent: CC(=O)O
Solvent: CO
Product: NC(=O)CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1
Reaction time: 72 h

Procedure:
1.0 g of L-pyroglutamyl-L-histidyl-L-prolyl-β-alanine methyl ester acetate was dissolved in 100 ml of methanol. The resulting solution was saturated with ammonia at 0° C, the vessel was made gas-tight and stored at room temperature for 3 days. The solution was then concentrated in vacuo, the residue dissolved in 50 ml of water and lyophilised. Yield: 900 mg. [α]D25 = -94.9° (c = 1 in 1 N acetic acid).
Reaction SMILES: [CH3:1][N:2]([CH:10]1[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].C1(C)C(S([CH2:26][N+:27]#[C-])(=O)=O)=CC=CC=1.CC(C)([O-])C.[K+]>O1CCCC1>[CH3:1][N:2]([CH:10]1[CH2:15][CH2:14][CH:13]([C:26]#[N:27])[CH2:12][CH2:11]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6]
Reactant: CN(C(=O)OC(C)(C)C)C1CCC(=O)CC1
Reactant: [C-]#[N+]CS(=O)(=O)c1ccccc1C
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CN(C(=O)OC(C)(C)C)C1CCC(C#N)CC1
Temperature: 0 °C
Reaction time: 3 h
Yield: 30 %

Procedure:
t-Butyl methyl-(4-oxocyclohexyl)carbamate (4.54 g, 20 mmol) and toluenesulphonylmethyl isocyanide (5.07 g, 26 mmol) were dissolved in dry tetrahydrofuran (100 ml) and cooled to 0° C. Potassium tert-butoxide (5.16 g, 46 mmol) was added slowly and the mixture was allowed to warm to 20° C. and stir for 3 hours. The reaction mixture was evaporated to dryness and partitioned between ethyl acetate (150 ml) and water (50 ml). The organic layer was separated, dried over magnesium sulfate and evaporated. The crude product was chromatographed on a silica gel eluting with ethyl acetate/hexane (66:34) to give 1.43 g of tert-butyl methyl-(4-cyanocyclohexyl)carbamate.
Reaction SMILES: [O:1]=[C:2]1[C:10](=[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]([CH2:20][CH2:21]OS(C)(=O)=O)[O:12]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.[CH2:27]([NH:29][CH2:30][CH3:31])[CH3:28].O1CCOCC1>C1COCC1>[CH2:27]([N:29]([CH2:30][CH3:31])[CH2:21][CH2:20][CH:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:11](=[C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[NH:3][C:2]2=[O:1])[O:12]1)[CH3:28]
Reactant: CCNCC
Reactant: CS(=O)(=O)OCCC1OC(=C2C(=O)Nc3ccccc32)c2ccccc21
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: CCN(CC)CCC1OC(=C2C(=O)Nc3ccccc32)c2ccccc21
Reaction time: 3 h
Yield: 70.2 %

Procedure:
A solution of methanesulfonic acid 2-[3-(2-oxo-1,2-dihydro-indol-3-ylidene)-1,3-dihydro-isobenzofuran-1-yl]-ethyl ester (50 mg, 0.135 mmol) and diethylamine (279 μl, 2.7 mmol) in THF (0.8 ml) was heated at 60° C. After 3 hours, dioxane (0.3 ml) was added to give a solution and the reaction continued at 60° C. for 24 h. The reaction was partitioned between EtOAc and water. The EtOAc layer was washed with water, brine, dried with anhydrous Na2SO4 and rotary evaporated to give brown oil. The brown oil was chromatographed (CHCl3 to 2% MeOH/CHCl3 gradient) to yield 3-[3-(2-diethylamino-ethyl)-3H-isobenzofuran-1-ylidene]-1,3-dihydro-indol-2-one as a yellow-green solid (33 mg, 71%).