Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:46]=[CH:45][C:7]([CH2:8][O:9][C:10]([NH:12][CH2:13][CH:14]([OH:44])[CH2:15][S:16][CH2:17][C@@H:18]2[CH2:22][C@@H:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:20][N:19]2[C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=2)=[O:32])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].N1C=CC=CC=1.[C:53](Cl)(=[O:55])[CH3:54]>ClCCl>[C:53]([O:44][CH:14]([CH2:13][NH:12][C:10]([O:9][CH2:8][C:7]1[CH:45]=[CH:46][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1)=[O:11])[CH2:15][S:16][CH2:17][C@@H:18]1[CH2:22][C@@H:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:25])[CH3:26])[CH2:20][N:19]1[C:31]([O:33][CH2:34][C:35]1[CH:36]=[CH:37][C:38]([N+:41]([O-:43])=[O:42])=[CH:39][CH:40]=1)=[O:32])(=[O:55])[CH3:54]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1C[C@@H](CSCC(O)CNC(=O)OCc2ccc([N+](=O)[O-])cc2)N(C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Reactant: CC(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)OC(CNC(=O)OCc1ccc([N+](=O)[O-])cc1)CSC[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1

Procedure:
To a solution of (2S,4R)-2-[3-(4-nitrobenzyloxycarbonyl)amino-2-hydroxypropyl]thiomethyl-4-t-butyldimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (2.24 g) in dichloromethane (40 ml) were added pyridine (0.52 ml) and acetyl chloride (0.46 ml) under ice-cooling with stirring. The mixture was stirred at the same temperature for 1 hour. The reaction mixture was washed with water, saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, in turn, dried over anhydrous magnesium sulfate, and evaporated in vacuo to give (2S,4R)-2-[2-acetoxy-3-(4-nitrobenzyloxycarbonyl)aminopropyl]thiomethyl-4-t-butyldimethylsilyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (2.37 g).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[Cl:16][CH2:17][C:18]([NH:20][C:21]1[CH:31]=[CH:30][C:24]([CH:25]=[CH:26][C:27](Cl)=[O:28])=[CH:23][CH:22]=1)=[O:19]>>[Cl:16][CH2:17][C:18]([NH:20][C:21]1[CH:31]=[CH:30][C:24]([CH:25]=[CH:26][C:27]([N:13]2[CH2:12][CH2:11][N:10]([CH2:9][CH2:8][C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH2:15][CH2:14]2)=[O:28])=[CH:23][CH:22]=1)=[O:19]
Reactant: O=C(Cl)C=Cc1ccc(NC(=O)CCl)cc1
Reactant: Clc1ccc(CCN2CCNCC2)cc1
Product: O=C(CCl)Nc1ccc(C=CC(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1

Procedure:
Analogously to Example 7, 1-[2-(4-chlorophenyl)ethyl]piperazine and 4-chloroacetylaminocinnamic acid chloride are reacted to form 1-{3-[4-(N-chloroacetylamino)phenyl]prop-2-en-1-on-yl}-4-[2-(4-chlorophenyl)ethyl]piperazine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.Cl[C:24](Cl)([O:26][C:27](=[O:33])OC(Cl)(Cl)Cl)Cl.[CH:35]1(CO)[CH2:37][CH2:36]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:27](=[O:33])[O:26][CH2:24][CH:35]2[CH2:37][CH2:36]2)=[CH:18][CH:17]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2ncnc(Oc3ccc(N)cc3)c2cc1OC
Reactant: OCC1CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1cc2ncnc(Oc3ccc(NC(=O)OCC4CC4)cc3)c2cc1OC
Yield: 90.2 %

Procedure:
4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, cyclopropylmethanol (19 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 75%).
Reaction SMILES: [CH3:1][S:2]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:13]3[N:14]([N:18]=[C:19]([NH2:21])[N:20]=3)[CH:15]=[CH:16][CH:17]=2)=[CH:8][CH:7]=1)(=[O:4])=[O:3].Br[C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[CH:25][CH:24]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:1][S:2]([CH2:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[C:13]3[N:14]([N:18]=[C:19]([NH:21][C:23]4[CH:24]=[CH:25][C:26]([N:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)=[CH:27][CH:28]=4)[N:20]=3)[CH:15]=[CH:16][CH:17]=2)=[CH:10][CH:11]=1)(=[O:3])=[O:4]
Reactant: CN1CCN(c2ccc(Br)cc2)CC1
Reactant: CS(=O)(=O)Cc1ccc(-c2cccn3nc(N)nc23)cc1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN1CCN(c2ccc(Nc3nc4c(-c5ccc(CS(C)(=O)=O)cc5)cccn4n3)cc2)CC1

Procedure:
A suspension of (4-bromomethylphenyl)boronic acid (2.0 g, 9.3 mmol) and sodium methanesulfinate (1.4 g, 14 mmol) in Ethanol (30 mL) was heated at 60° C. for 24 hours. The mixture was evaporated to dryness and the residue was suspended in water. The precipitate was filtered, rinsed with water and air dried. The reaction product was isolated as an off-white solid (1.18 g, 59%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.09 (s, 2H), 7.79 (d, J=7.9 Hz, 2H), 7.37 (d, J=7.9 Hz, 2H), 4.47 (s, 2H), 2.88 (s, 3H). MS=135 (M—SO2CH3)+. 48b) 8-(4-Methanesulfonylmethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine was prepared from 8-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (200.0 mg, 0.9388 mmol) and (4-methanesulfonylmethylphenyl)boronic acid (240.0 mg, 1.121 mmol) with Pd(dppf)Cl2 (130.0 mg) as the catalyst in a manner analogous to Step 2c. The reaction product was isolated as a pale yellow solid (0.051 g, 18%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.56 (dd, J=6.6, 1.0 Hz, 1H), 8.12 (d, J=8.3 Hz, 2H), 7.73 (dd, J=7.5, 1.0 Hz, 1H), 7.52 (d, J=8.3 Hz, 2H), 6.99 (dd, J=7.3, 7.3 Hz, 1H), 6.11 (s, 1H), 4.55 (s, 2H), 2.94 (s, 3H). MS=303 (MH)+. 48c) [8-(4-Methanesulfonylmethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine was prepared from 8-(4-methanesulfonylmethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (50.0 mg, 0.165 mmol) and 1-(4-bromo-phenyl)-4-methyl-piperazine (51.0 mg, 0.200 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (20.0 mg, 0.0366 mmol) as the ligand in a manner analogous to Step 2d. The title compound was isolated as a yellow foam (0.009 g, 11%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.44-8.40 (m, 1H), 8.08 (d, J=8.1 Hz, 2H), 7.60-7.54 (m, 3H), 7.51-7.46 (m, 2H), 7.00-6.93 (m, 3H), 6.70 (s, 1H), 4.32 (s, 2H), 3.21-3.14 (m, 4H), 2.83 (s, 3H), 2.66-2.56 (m, 4H), 2.37 (s, 3H). MS=477 (MH)+.
Reaction SMILES: C(OC)(=O)C1C=CC(C([O-])=O)=CC=1.[K+:14].[C:15]([O:28]CC)(=[O:27])[C:16]1[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][CH:17]=1.[OH-].[K+].C1(C)C=CC=CC=1>C(O)C>[C:20]([O:22][CH2:23][CH3:24])(=[O:21])[C:19]1[CH:25]=[CH:26][C:16]([C:15]([O-:28])=[O:27])=[CH:17][CH:18]=1.[K+:14]
Reactant: CCOC(=O)c1ccc(C(=O)OCC)cc1
Agent: COC(=O)c1ccc(C(=O)[O-])cc1
Agent: [K+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCOC(=O)c1ccc(C(=O)[O-])cc1

Procedure:
This compound was prepared by the procedure described for potassium monomethyl terephthalate. Typical reagent levels were as follows: 77.0 gm (0.346 mole) of diethyl terephthalate, 19.4 gm of potassium hydroxide, 150 ml of toluene and 100 ml of ethanol.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=O)=[CH:13][CH:14]=3)[C:9]([CH3:18])=[N:8]2)=[C:4]([C:21]([F:24])([F:23])[F:22])[CH:3]=1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][N:35]([C:38]2[S:39][CH2:40][C:41](=[O:43])[N:42]=2)[CH2:34][C@@H:33]1[CH2:44][OH:45])=[O:31])([CH3:28])([CH3:27])[CH3:26]>>[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][N:35]([C:38]2[S:39][C:40](=[CH:16][C:12]3[CH:11]=[C:10]4[C:15](=[CH:14][CH:13]=3)[N:7]([CH2:6][C:5]3[CH:19]=[CH:20][C:2]([Cl:1])=[CH:3][C:4]=3[C:21]([F:24])([F:22])[F:23])[N:8]=[C:9]4[CH3:18])[C:41](=[O:43])[N:42]=2)[CH2:34][C@@H:33]1[CH2:44][OH:45])=[O:31])([CH3:28])([CH3:27])[CH3:26]
Reactant: CC(C)(C)OC(=O)N1CCN(C2=NC(=O)CS2)C[C@@H]1CO
Reactant: Cc1nn(Cc2ccc(Cl)cc2C(F)(F)F)c2ccc(C=O)cc12
Product: Cc1nn(Cc2ccc(Cl)cc2C(F)(F)F)c2ccc(C=C3SC(N4CCN(C(=O)OC(C)(C)C)[C@@H](CO)C4)=NC3=O)cc12

Procedure:
4-{5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-3-methyl-1H-indazol-5-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-yl}-2-(R)-hydroxymethyl-piperazine-1-carboxylic acid tert-butyl ester was prepared from 1-(4-Chloro-2-trifluoromethyl-benzyl)-3-methyl-1H-indazole-5-carbaldehyde and 2-(R)-Hydroxymethyl-4-(4-oxo-4,5-dihydro-thiazol-2-yl)-piperazine-1-carboxylic acid tert-butyl ester following general procedure D.
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[CH:10]=[C:11](N)[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1.[O:21]1CCCC1.C(O)C.[OH-].[Na+]>O.C(O)(=O)C>[CH3:1][NH:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[CH2:10][C:11](=[O:21])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1
Reactant: CNC(=O)c1cccnc1C=C(N)c1ccc(Cl)cc1
Reactant: C1CCOC1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CCO
Solvent: O
Product: CNC(=O)c1cccnc1CC(=O)c1ccc(Cl)cc1
Temperature: 40 °C
Reaction time: 4 h

Procedure:
22 g. (76.5 mmol.) of 2-(4'-chloro-β-aminostyryl)nicotinic acid N-methylamide (Compound XIX) were dissolved in 80 ml. of tetrahydrofuran and 40 ml. of ethanol and a mixture of 40 ml. of acetic acid and 40 ml. of water was added. The reaction mixture was stirred at 40° C. for 4 hours. The reaction mixture was then made basic to pH 9 with sodium hydroxide solution and extracted with diethyl ether, ethyl acetate and methylene chloride. The three organic extracts were combined, treated with charcoal, dried over anhydrous magnesium sulfate and concentrated at reduced pressure to obtain a yellow solid which was recrystallized from ethanol to obtain the product as a yellow green solid, m.p. 162°-163° C.
Reaction SMILES: C1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([CH3:18])[C:10](=[O:19])[CH:9]([NH:20][C:21]([O:23]C3C=CC([N+]([O-])=O)=CC=3)=O)[N:8]=2)CCCCC1.C(N([CH2:38][CH3:39])CC)C.[NH2:40][C:41]1[CH:42]=[CH:43][C:44]2[CH2:49][S:48](=[O:51])(=[O:50])[NH:47][C:46](=[O:52])[C:45]=2[CH:53]=1>CN(C)C=O.C(#N)C>[CH2:39]1[CH2:38][CH:7]([C:9]2([NH:20][C:21]([NH:40][C:41]3[CH:42]=[CH:43][C:44]4[CH2:49][S:48](=[O:51])(=[O:50])[NH:47][C:46](=[O:52])[C:45]=4[CH:53]=3)=[O:23])[N:8]=[CH:7][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([CH3:18])[C:10]2=[O:19])[CH2:13][CH2:12][CH2:17]1
Reactant: Nc1ccc2c(c1)C(=O)NS(=O)(=O)C2
Reactant: CN1C(=O)C(NC(=O)Oc2ccc([N+](=O)[O-])cc2)N=C(C2CCCCC2)c2ccccc21
Reactant: CCN(CC)CC
Solvent: CC#N
Solvent: CN(C)C=O
Product: CN1C(=O)C(NC(=O)Nc2ccc3c(c2)C(=O)NS(=O)(=O)C3)(C2CCCCC2)N=Cc2ccccc21
Temperature: 50 °C
Reaction time: 0.08 h
Yield: 73.1 %

Procedure:
To a solution of 5-cyclohexyl-1,3-dihydro-1-methyl-3(R,S)-[(4-nitrophenyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one (22 mg, 0.51 mmol) in anhydrous dimethylformamide (3 ml) under nitrogen was added triethylamine (70 μl, 0.51 mmol). The solution was stirred for 5 min before adding a solution of 6-amino-3,4-dihydro-2,2-dioxo-4-oxo-1H-2,3-benzothiazine (107 mg, 0.51 mmol) and triethylamine (70 μl, 0.51 mmol) in anhydrous dimethylformamide (3 ml) and acetonitrile (10 ml). The resulting solution was heated at 50° C. for 10 h, before removing the solvents in vacuo and partitioning the residue between 20% aqueous acetic acid (5 ml) and ethyl acetate (20 ml). The aqueous phase was re-extracted with more ethyl acetate (2×20 ml) and the combined organic extracts dried (Na2SO4) and evaporated in vacuo. The resulting yellow oil was stirred with diethyl ether (10 ml) to give a pale yellow solid. This was purified by flash chromatography on silica gel, eluting with 5-20% methanol/dichloromethane, to afford the title compound (95 mg, 37%) as a pale yellow solid, which was recrystallised from isopropanol/dichloromethane. mp>300° C. 1H NMR (360 MHz, D6-DMSO) δ 0.93 (1H, m), 1.12-1.64 (7H, m), 1.76 (1H, m), 1.89 (1H, m), 2.93 (1H, m), 3.29 (3H, s), 3.96 (2H, s), 5.08 (1H, d, J=8.4 Hz), 7.09 (1H, d, J=8.3 Hz), 7.24 (1H, d, J =8.5 Hz), 7.38 (1H, t, J=7.9 Hz), 7.49 (1H, dd, J=8.2 and 2.4 Hz), 7.55 (1H, d, J=8.3 Hz), 7.63 (1H, t, J=7.9 Hz), 7.74-7.76 (2H, m), 9.04 (1H, s). MS (FAB) 508 (M-1).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[C:17]([CH:33]=[O:34])=[C:18]([N:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:24]([C:31]#[N:32])=[CH:23]3)[CH:19]=[CH:20][CH:21]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].BrC1C(C=[O:54])=C(N2C3C(=CC=CC=3)C(C#N)=C2)C=CC=1>>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[C:17]([CH2:33][OH:34])=[C:18]([N:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:24]([C:31]([NH2:32])=[O:54])=[CH:23]3)[CH:19]=[CH:20][CH:21]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]
Reactant: N#Cc1cn(-c2cccc(Br)c2C=O)c2ccccc12
Reactant: CC(C)(C)c1ccc2c(=O)n(-c3cccc(-n4cc(C#N)c5ccccc54)c3C=O)ncc2c1
Product: CC(C)(C)c1ccc2c(=O)n(-c3cccc(-n4cc(C(N)=O)c5ccccc54)c3CO)ncc2c1
Yield: 66 %

Procedure:
The preparation of 1-(3-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-2-formylphenyl)-1H-indole-3-carbonitrile, via reaction of 1-(3-bromo-2-formylphenyl)-1H-indole-3-carbonitrile (222 mg, 40% pure, 0.27 mmol, synthesis described above in Example 18, step 1) with 6-tert-butylphthalzin-1(2H)-one (138 mg, 0.68 mmol) was carried out in a procedure analogous to that described in Example 18. Similar work up and purification provided desired product as a light yellow-white solid (82 mg, 66% yield). LC/MS calcd for C28H22N4O2 (m/e) 446.51, obsd 447.0 (M+H, ES+): 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 9H) 7.23-7.40 (m, 3H) 7.55 (dd, J=7.93, 1.13 Hz, 2H) 7.72-7.94 (m, 6H) 8.32 (s, 1H) 8.39 (d, J=8.31 Hz, 1H) 9.59 (s, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[CH3:16][O:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]([O:26][CH3:27])[CH:19]=1>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH:13]=[C:12]([C:19]3[C:20]([O:26][CH3:27])=[CH:21][C:22]([O:24][CH3:25])=[CH:23][C:18]=3[O:17][CH3:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1
Reactant: COc1cc(OC)cc(OC)c1
Reactant: COc1ccc(N2CCC(=O)CC2)cc1
Solvent: CC(=O)O
Product: COc1ccc(N2CC=C(c3c(OC)cc(OC)cc3OC)CC2)cc1
Temperature: 90 °C

Procedure:
Compound of example 117 (19.0 g, 92 mmol) was added to a solution of 1,3,5-trimethoxybenzene (21.8 g, 130 mmol) in glacial acetic acid (50 mL) at 25° C. HCl gas was bubbled through the reaction mixture for 1 h, slowly raising the temperature up to 90° C. Acetic acid was removed under reduced pressure and the semisolid residue was poured over crushed ice (300 g). The resulting solution was made basic using an aqueous 50% NaOH solution. The precipitated solid was filtered, washed with water and dried. The solid was added slowly to boiling methanol, stirred for fifteen minutes and filtered to remove traces of trimethoxybenzene and the filtrate was concentrated to get the title compound.
Reaction SMILES: [NH2:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]1=[O:12].[F:18][C:19]([F:26])([F:25])[C:20](SCC)=[O:21]>CO>[F:18][C:19]([F:26])([F:25])[C:20]([NH:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]1=[O:12])=[O:21]
Reactant: CCSC(=O)C(F)(F)F
Reactant: N[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1ccc(=O)[nH]c1=O
Solvent: CO
Product: O=C(N[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1n1ccc(=O)[nH]c1=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 8 h
Yield: 82.5 %

Procedure:
To a suspension of 2'-amino,2'-deoxyuridine (2.0 g, 8.22 mmoles) in methanol (150 ml) was added S-ethyl trifluorothioacetate (1.6 ml, 12.48 mmoles, 1.5 eq.). This mixture was stirred at room temperature overnight. Nitrogen was bubbled through the reaction mixture for 2 h to remove volatile thio-byproducts. The mixture was evaporated to dryness and the solid was recrystallized from methanol/chloroform to yield 2.3 g (82%) of 2'-trifluoroacetylamino,2'-deoxyuridine. The analytical data agreed with the literature (Imazawa and Eckstein (1979) supra).
Reaction SMILES: [CH3:1][C:2]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[N:12]([O-])=O.[Na+].O.N>C(O)(=O)C>[N+:9]([C:8]1[CH:7]=[CH:6][CH:5]=[C:3]2[C:2]=1[CH:1]=[N:12][NH:4]2)([O-:11])=[O:10]
Reactant: O=N[O-]
Reactant: Cc1c(N)cccc1[N+](=O)[O-]
Agent: N
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: O=[N+]([O-])c1cccc2[nH]ncc12
Temperature: 25 °C
Reaction time: 5 h

Procedure:
A solution of 2-methyl-3-nitro aniline (1 mmol) in acetic acid was stirred at room temperature and sodium nitrite (1.1 mmol) was added to the reaction mixture. Reaction mixture was stirred at room temperature for 5 hours. Reaction mixture was poured into water and neutralized with ammonia. Product precipitated out, was filtered and washed with water. It was then purified by column chromatography to afford the desired compound as a pale yellow solid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH2:12][N:11](C(OCC2C=CC=CC=2)=O)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CCO.[Pd]>[NH:11]1[CH2:12][CH2:13][CH2:14][CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:10]1
Reactant: CC(C)(C)OC(=O)NC1CCCN(C(=O)OCc2ccccc2)C1
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)NC1CCCNC1
Temperature: 25 °C
Reaction time: 14 h
Yield: 90.5 %

Procedure:
A mixture of benzyl 3-[(tert-butoxycarbonyl)amino]-1-piperidinecarboxylate (2.25 g, 6.73 mmol) and 10% Pd/C (0.229 g) in EtOH (20 mL) was stirred at room temperature under a hydrogen atmosphere (1 atm) for 14 hrs. The catalyst was removed by filtration through Celite®, and the filtrate was concentrated under reduced pressure to give tert-butyl 3-piperidinylcarbamate as a solid (1.22 g, yield; 91%).
Reaction SMILES: [CH2:1]([NH:3][CH2:4][CH:5]1[O:9][CH2:8][CH2:7][O:6]1)[CH3:2].C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:22][CH2:23][C:24](Cl)=[O:25]>O>[CH2:1]([N:3]([CH2:4][CH:5]1[O:9][CH2:8][CH2:7][O:6]1)[C:24](=[O:25])[CH2:23][Cl:22])[CH3:2]
Reactant: CCNCC1OCCO1
Reactant: O=C(Cl)CCl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: c1ccccc1
Product: CCN(CC1OCCO1)C(=O)CCl

Procedure:
N-Ethyl-N-(1,3-dioxolan-2-ylmethyl)amine (50 grams), benzene (100 ml), water (100 ml) and sodium carbonate (5.0 grams) were charged into a glass reaction vessel equipped with a mechanical stirrer and reflux condenser. The mixture was cooled to about 5° to 10° C. and chloroacetyl chloride (3 ml) was added dropwise with stirring. After the addition was completed stirring was continued until the reaction mixture reached room temperature. After this time the organic phase was separated from the aqueous phase and was washed with water. The washed solution was then dried over anhydrous magnesium sulfate, filtered and stripped of solvent under reduced pressure to yield the desired product N-ethyl-N-(1,3-dioxolan-2-ylmethyl)-α-chloroacetamide as an oil.
Reaction SMILES: C([N:8](CC1C=CC=CC=1)[NH:9][C:10](=[O:31])[C:11]1[CH:16]=[C:15]([N:17]([CH3:19])[CH3:18])[CH:14]=[C:13]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=2)[N:12]=1)C1C=CC=CC=1.[H][H]>[Pd].CO>[CH3:18][N:17]([CH3:19])[C:15]1[CH:14]=[C:13]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=2)[N:12]=[C:11]([C:10]([NH:9][NH2:8])=[O:31])[CH:16]=1
Reactant: CN(C)c1cc(Oc2cccc(C(F)(F)F)c2)nc(C(=O)NN(Cc2ccccc2)Cc2ccccc2)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CN(C)c1cc(Oc2cccc(C(F)(F)F)c2)nc(C(=O)NN)c1

Procedure:
4-dimethylamino-6-[3-(trifluoromethyl)phenoxy] picolinic acid, N',N'-dibenzyl hydrazide (0.80 g, 0.00154 mol) was mixed with methanol (about 10 ml), and further with 10% palladium/carbon (0.2 g, 0.00154×0.12 mol) in a hydrogen atmosphere (about 0.5 kg/cm2). The resultant mixture was stirred at a temperature of about 50 to 60° C. for about 3 hours. The obtained reaction solution was filtered and concentrated, thereby obtaining an aimed product.
Reaction SMILES: C(OC([N:11]1[CH2:15][C@H:14]([CH2:16][CH3:17])[C@H:13]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:12]1)=O)C1C=CC=CC=1.[H][H]>[C].[Pd].CO>[C:22]([O:21][C:19]([NH:18][C@H:13]1[C@@H:14]([CH2:16][CH3:17])[CH2:15][NH:11][CH2:12]1)=[O:20])([CH3:25])([CH3:24])[CH3:23]
Reactant: CC[C@H]1CN(C(=O)OCc2ccccc2)C[C@H]1NC(=O)OC(C)(C)C
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CC[C@H]1CNC[C@H]1NC(=O)OC(C)(C)C

Procedure:
A 10% palladium carbon catalyst (50 mg) was added to a solution of (3S,4S)-1-benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-ethylpyrrolidine (514 mg, 1.48 mmol) in methanol (15 mL). The resultant mixture was stirred at room temperature for 2 hours under an ordinary pressure in a hydrogen atmosphere. After filtration, the filtrate was concentrated under reduced pressure, to thereby yield the title compound as a colorless oily substance (324 mg, quantitative amount).
Reaction SMILES: [CH2:1]([NH2:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH2:10]([N:14]=[C:15]=[O:16])[CH2:11][CH2:12][CH3:13].Cl.[F:18][B-:19]([F:22])([F:21])[F:20].[Na+]>C(OCC)(=O)C.CO>[F:18][B-:19]([F:22])([F:21])[F:20].[CH2:10]([NH:14][C:15]([NH:9][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])=[O:16])[CH2:11][CH2:12][CH3:13]
Reactant: CCCCCCCCN
Reactant: CCCCN=C=O
Agent: Cl
Agent: F[B-](F)(F)F
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCCCCCCCNC(=O)NCCCC
Temperature: 10 °C
Reaction time: 0.5 h
Yield: 97 %

Procedure:
A four necked flask equipped with a thermometer, stirrer and drip funnel was charged with 2.58 g of octylamine and 200 g of ethyl acetate. To this was added dropwise a solution of 1.98 g of n-butylisocyanate in 30 g of ethyl acetate with stirring over 30 minutes while maintaining the inner temperature at 10° C. and allowed to react until the absorption of isocyanato group (2240 cm-1) disappeared IR spectrometrically. After dissolving the solidified reaction product in 50 g of methanol, a mixture of 2.086 g of 35% hydrochloric acid and 50 g of methanol was added dropwise to the solution over 30 minutes and allowed to react at room temperature for 20 hours. Then a solution of 2.2 g of sodium tetrafluoroborate in 50 g of methanol was added dropwise over 30 minutes and allowed to react at room temperature for 20 hours. The reaction mixture was then filtered to remove NaCl by-product and evaporated to remove the solvent. 6.1 g of the title compound was obtained as a pale yellow liquid.