Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:5]1[N:10]=[C:9]([CH3:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[C:7](=[O:19])[C:6]=1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:33]2[NH:37][C:36](=[O:38])[O:35][N:34]=2)=[CH:23][CH:22]=1)[CH2:2][CH2:3][CH3:4].[CH3:39][CH:40]1[CH2:45][CH:44](O)[CH2:43][CH2:42][O:41]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.O>[CH2:1]([C:5]1[N:10]=[C:9]([CH3:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH:44]3[CH2:43][CH2:42][O:41][CH:40]([CH3:39])[CH2:45]3)=[CH:14][CH:13]=2)[C:7](=[O:19])[C:6]=1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[C:33]2[NH:37][C:36](=[O:38])[O:35][N:34]=2)=[CH:23][CH:22]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(C)n(-c2ccc(O)cc2)c(=O)c1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Reactant: CC1CC(O)CCO1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: CCCCc1nc(C)n(-c2ccc(OC3CCOC(C)C3)cc2)c(=O)c1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Reaction time: 2 h
Yield: 60.4 %

Procedure:
To a solution of 6-butyl-3-(4-hydroxyphenyl)-2-methyl-5-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-one (0.5 g), 2-methyltetrahydro-2H-pyran-4-ol (0.26 g) and triphenylphosphine (0.58 g) in tetrahydrofuran (5 mL) was added dropwise diisopropyl azodicarboxylate (1.9 M toluene solution, 1.2 mL). After stirring for 2 hr, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and a mixture of the residue, hydroxylammonium chloride (0.77 g), sodium hydrogen carbonate (1.1 g) and dimethyl sulfoxide (10 mL) was stirred overnight at 90° C. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL). N,N′-carbonyldiimidazole (0.27 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.25 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound (0.36 g, 53%) as an amorphous solid.
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl[C:22]([O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:23]>>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:22](=[O:23])[O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][CH:12]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1cc(N)n(-c2ccc(C(F)(F)F)cc2)n1
Reactant: O=C(Cl)Oc1ccccc1
Product: CC(C)(C)c1cc(NC(=O)Oc2ccccc2)n(-c2ccc(C(F)(F)F)cc2)n1
Yield: 58.3 %

Procedure:
The title compound was prepared from 3-tert-butyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-5-amine (1.36 g, 4.80 mmol) and phenyl chloroformate (1.82 mL, 14.4 mmol) using the procedure in Example 118A to give phenyl 3-tert-butyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-5-ylcarbamate (113 mg, 2.80 mmol, 58%). 1H NMR (300 MHz, DMSO-d6) δ 10.20 (br s, 1H), 7.93 (d, 2H), 7.81 (d, 2H), 7.40-7.10 (m, 5H), 6.44 (s, 1H), 1.29 (s, 9H); LC-MS (ESI) m/z 404 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][CH2:5][C:4]2[CH:9]=[C:10]([N+:13]([O-])=O)[CH:11]=[CH:12][C:3]1=2.O.NN>[Pd].C(O)C>[CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][CH2:5][C:4]2[CH:9]=[C:10]([NH2:13])[CH:11]=[CH:12][C:3]1=2
Reactant: CN1CCCCc2cc([N+](=O)[O-])ccc21
Agent: [Pd]
Agent: NN
Solvent: O
Solvent: CCO
Product: CN1CCCCc2cc(N)ccc21
Temperature: 60 °C
Yield: 94.6 %

Procedure:
1-Methyl-7-nitro-2,3,4,5-tetrahydro-1H-benzo[b]azepine (135 mg, 0.66 mmol) in a solution of ethanol (4 mL) and hydrazine hydrate (1 mL) was treated with 10% palladium on carbon (40 mg) and heated at 60° C. for 2 h. The mixture was cooled to room temperature, filtered and concentrated to give 1-Methyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamine (110 mgs, 96%) as a grayish oil.; 1H-NMR (CDCl3) δ 6.78-6.72 (m, 1H), 6.51 (s, 2H), 3.38 (br s, 2H), 2.82-2.74 (m, 7H), 2.21-2.15 (m, 2H), 1.75-1.68 (m, 2H), 1.57-1.52 (m, 2H); LC/MS (ESI+): 177.16 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[I:9].[C:10]([C:13]1[S:17][C:16]([C:18](O)=[O:19])=[CH:15][CH:14]=1)(=[O:12])[CH3:11]>>[C:10]([C:13]1[S:17][C:16]([C:18]([NH:6][C:5]2[CH:7]=[CH:8][C:2]([Cl:1])=[C:3]([I:9])[CH:4]=2)=[O:19])=[CH:15][CH:14]=1)(=[O:12])[CH3:11]
Reactant: CC(=O)c1ccc(C(=O)O)s1
Reactant: Nc1ccc(Cl)c(I)c1
Product: CC(=O)c1ccc(C(=O)Nc2ccc(Cl)c(I)c2)s1

Procedure:
4-Chloro-3-iodoaniline (2.5 g, 9.88 mmol) was used in Procedure E with 5-acetylthiophene-2-carboxylic acid (1.85 g, 10.8 mmol) at 23° C. for 2 hours. The crude material was purified by silica gel chromatography (20-100% ethyl acetate/hexanes) to yield 5-Acetyl-N-(4-chloro-3-iodophenyl)thiophene-2-carboxamide as a yellow solid.
Reaction SMILES: Cl.Cl.[C:3]([C:11]1[CH:16]=[CH:15][C:14]([CH:17]([CH3:26])[CH2:18][N:19]2[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]2)=[CH:13][CH:12]=1)(=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.[CH:34]1([C:37](Cl)=[O:38])[CH2:36][CH2:35]1>C(Cl)Cl>[C:3]([C:11]1[CH:16]=[CH:15][C:14]([CH:17]([CH3:26])[CH2:18][N:19]2[CH2:24][CH2:23][CH:22]([NH:25][C:37]([CH:34]3[CH2:36][CH2:35]3)=[O:38])[CH2:21][CH2:20]2)=[CH:13][CH:12]=1)(=[O:10])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: CC(CN1CCC(N)CC1)c1ccc(C(=O)c2ccccc2)cc1
Reactant: O=C(Cl)C1CC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(CN1CCC(NC(=O)C2CC2)CC1)c1ccc(C(=O)c2ccccc2)cc1

Procedure:
A stirred solution of 1-[2-(4-benzoylphenyl)propyl]-4-aminopiperidine dihydrochloride, 150 ml. of methylene dichloride and 10.5 g. (0.105 mole) of triethylamine was treated in portions with a solution of 3.9 g. (0.039 mole) of cyclopropanecarbonyl chloride in methylene dichloride. When addition was complete the mixture was allowed to stand at ambient temperature for twenty-four hours and then washed two times with water, once with aqueous potassium carbonate and once with brine and then dried and taken to dryness in vacuo. Recrystallization of the residue from diethyl ether gave 1-[2-(4-benzoylphenyl)propyl]-4-cyclopropanecarbonylaminopiperidine, m.p. 159°-160° C.
Reaction SMILES: [F:1][C:2]1[C:3]([NH:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])=[N:4][C:5]([OH:8])=[N:6][CH:7]=1.[C:19]1([S:25](Cl)(=[O:27])=[O:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CC#N>[C:19]1([S:25]([N:6]2[CH:7]=[C:2]([F:1])[C:3]([NH:9][C:10]([NH:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[O:11])=[N:4][C:5]2=[O:8])(=[O:27])=[O:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: O=C(Nc1ccccc1)Nc1nc(O)ncc1F
Solvent: CC#N
Product: O=C(Nc1ccccc1)Nc1nc(=O)n(S(=O)(=O)c2ccccc2)cc1F
Temperature: 70 °C
Reaction time: 1 h
Yield: 32.2 %

Procedure:
To a suspension of 1-(5-fluoro-2-hydroxypyrimidin-4-yl)-3-phenylurea (0.200 g, 0.8 mmol) in anhydrous CH3CN (4 mL) was added BSA (0.487 g, 2.4 mmol), and the mixture was warmed to 70° C. and stirred for 1 h. The resulting solution was cooled to room temperature, treated with benzenesulfonyl chloride (0.156 g, 0.9 mmol), and the mixture was stirred for 12 h. The solvent was evaporated, and the residue was partitioned between EtOAc and brine. The organic phase was dried over MgSO4, filtered, and concentrated to give the crude product as a white solid. Recrystallization from EtOAc and heptane afforded 1-(1-benzenesulfonyl-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)-3-phenylurea as a white solid (0.100 g, 32%): mp 210-214° C.; 1H NMR (400 MHz, DMSO-d6) δ 11.26 (dd, J=3.7, 1.1 Hz, 1H), 10.87 (m, 1H), 8.65 (m, 1H), 8.10 (d, J=7.5 Hz, 2H), 7.85 (t, J=7.5 Hz, 1H), 7.71 (m, 2H), 7.45 (m, 2H), 7.34 (m, 2H), 7.10 (m, 1H); ESIMS m/z 389 ([M+H]+).
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH3:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8]([CH:13]([CH3:16])[CH:14]=[CH2:15])[CH:7]=1>O>[C:1]([O:12][C:9]1[CH:10]=[CH:11][C:6]([CH3:5])=[CH:7][C:8]=1[CH:13]([CH3:16])[CH:14]=[CH2:15])(=[O:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: C=CC(C)c1cc(C)ccc1O
Solvent: O
Product: C=CC(C)c1cc(C)ccc1OC(C)=O
Reaction time: 2 h

Procedure:
42.6 ml (0.6 mole) of acetyl chloride are added dropwise in the course of 1 hour at room temperature, while stirring, to 81.1 g (0.5 mole) of 4-methyl-2-(1-methyl-2-propenyl)-phenol. The reaction mixture is then heated to 100° and left at this temperature for 2 hours. After cooling, water is cautiously added and extraction is carried out with methylene chloride. The organic phase is dried over sodium sulphate and concentrated by evaporation. Subsequent distillation of the remaining residue (64°-70°/4.10-2 torr) yields 4-methyl-2-(1-methyl-2-propenyl)-phenyl acetate in the form of a pale-yellow oil.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([S:26]([C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)(=[O:28])=[O:27])=[N:8][C:9]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:10]([N+:17]([O-])=O)[C:11]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:5])[CH3:2].C(O)(=O)C>C(O)C>[NH2:17][C:10]1[C:9]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:8][C:7]([S:26]([C:29]2[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=2)(=[O:28])=[O:27])=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[C:11]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13]
Reactant: CCOC(=O)c1c(S(=O)(=O)c2ccc(C)cc2)nc(-c2ccccc2)c([N+](=O)[O-])c1C(=O)OCC
Solvent: CCO
Solvent: CC(=O)O
Product: CCOC(=O)c1c(S(=O)(=O)c2ccc(C)cc2)nc(-c2ccccc2)c(N)c1C(=O)OCC
Temperature: 80 °C
Reaction time: 4.5 h
Yield: 43.8 %

Procedure:
In 10 ml of ethanol was suspended 0.35 g of 3,4-diethoxycarbonyl-5-nitro-6-phenyl-2-(p-tolylsulfonyl)pyridine, whereto 2 ml of acetic acid and 0.15 g of reduced iron were added. The mixture was stirred at 80° C. for 4.5 hours. After ethanol was distilled off, the residue was neutralized with an aqueous solution of sodium hydrogencarbonate, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over sodium sulfate, followed by concentration under reduced pressure. The residue was subjected to silica gel flash column chromatography with chloroform/ethyl acetate (4:1) as the eluent, to give 0.144 g of the title compound.
Reaction SMILES: C([O:5][C:6](=[O:18])[CH2:7][NH:8][C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)(C)(C)C.[CH2:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH:20]1[CH2:28]O>>[CH2:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH:20]1[CH2:28][O:16][C:13]1[CH:12]=[CH:11][C:10]([C:9]([NH:8][CH2:7][C:6]([OH:5])=[O:18])=[O:17])=[CH:15][CH:14]=1
Reactant: OCC1Cc2ccccc2C1
Reactant: CC(C)(C)OC(=O)CNC(=O)c1ccc(O)cc1
Product: O=C(O)CNC(=O)c1ccc(OCC2Cc3ccccc3C2)cc1
Yield: 85 %

Procedure:
The same reaction as in Example 1 (1b) was conducted using N-(4-hydroxybenzoyl)glycine tert-butyl ester (250 mg, 0.995 mmol) prepared in Example 1 (1a) and 2,3-dihydro-1H-inden-2-ylmethanol (which is the compound disclosed in J. Med. Chem., (1989), 32, 1326-1334, 165 mg, 1.11 mmol) to give 263 mg of the title compound (colorless crystalline solid, yield: 85%).
Reaction SMILES: O[CH:2]1[CH:7]([C:8](=[S:11])[NH:9][CH3:10])[C:6]2[CH:12]=[C:13]([N+:16]([O-:18])=[O:17])[CH:14]=[CH:15][C:5]=2[O:4][C:3]1([CH2:20][O:21][CH3:22])[CH3:19].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>C(OCC)(=O)C>[CH3:22][O:21][CH2:20][C:3]1([CH3:19])[CH:2]=[C:7]([C:8](=[S:11])[NH:9][CH3:10])[C:6]2[CH:12]=[C:13]([N+:16]([O-:18])=[O:17])[CH:14]=[CH:15][C:5]=2[O:4]1
Reactant: CNC(=S)C1c2cc([N+](=O)[O-])ccc2OC(C)(COC)C1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Solvent: O
Product: CNC(=S)C1=CC(C)(COC)Oc2ccc([N+](=O)[O-])cc21
Yield: 70.6 %

Procedure:
A mixture of 0.9 g of 3,4-dihydro-3-hydroxy-2-methoxymethyl-N,2-dimethyl-6-nitro-2H-1-benzopyran-4-carbothioamide, 0.12 g of p-toluenesulfonic acid monohydrate and 25 ml of toluene was refluxed with heating for 2 hours. Ethyl acetate was added to the mixture. After it was washed with water and dried, the solvent was distilled. The resultant residue was purified according to silica gel column chromatography (developing solution. MeOH:CH2Cl2 =1:99) to obtain 600 mg of 2-methoxymethyl-N,2-dimethyl-6-nitro-2H-1-benzopyran-4-carbothioamide with a melting point of 146°-148° C.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])=[O:9])=[CH:6][CH:5]=[C:4](Cl)[N:3]=1.FC(F)(F)C(O)=O.[CH3:26][S:27]([N:30]1[CH2:35][CH2:34][CH:33]([NH2:36])[CH2:32][CH2:31]1)(=[O:29])=[O:28].C(N(CC)C(C)C)(C)C>C(O)C>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])=[O:9])=[CH:6][CH:5]=[C:4]([NH:36][CH:33]2[CH2:34][CH2:35][N:30]([S:27]([CH3:26])(=[O:29])=[O:28])[CH2:31][CH2:32]2)[N:3]=1
Reactant: COc1ccccc1C(=O)c1ccc(Cl)nc1N
Reactant: CS(=O)(=O)N1CCC(N)CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Solvent: O=C(O)C(F)(F)F
Product: COc1ccccc1C(=O)c1ccc(NC2CCN(S(C)(=O)=O)CC2)nc1N
Temperature: 170 °C
Yield: 58.7 %

Procedure:
A mixture of (2-Amino-6-chloro-pyridin-3-yl)-(2-methoxy-phenyl)-methanone (24.9 mg, 0.0948 mmol, Example 5), 1-methanesulfonyl-piperidin-4-ylamine (50.6 mg, 0.284 mmol, from Step A above), N,N-diisopropylethylamine (38mg, 0.294 mmol) and ethanol (2.7 mL) were heated at 160-180° C. in a sealed tube under microwave conditions for 0.5-4 hrs. The resulting reaction mixture was concentrated in vacuo and the residue was purified on silica gel with methylene chloride/methanol to give [2-Amino-6-(1-methanesulfonyl-piperidin4-ylamino)-pyridin-3-yl]-(2-methoxy-phenyl)-methanone as a white solid (22.5 mg, 58% yield). HRMS, observed: 405.1594, calcd for (M+H)+: 405.1591.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18](/[CH:21]=[CH:22]/[CH:23]=[CH:24]/[CH:25]=O)=[CH:17][CH:16]=1.[O:27]1[CH2:31][C:30](=[O:32])[NH:29][C:28]1=[O:33].N1CCCCC1>C(O)(=O)C>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18](/[CH:21]=[CH:22]/[CH:23]=[CH:24]/[CH:25]=[C:31]2[O:27][C:28](=[O:33])[NH:29][C:30]2=[O:32])=[CH:17][CH:16]=1
Reactant: O=C1COC(=O)N1
Reactant: Cc1oc(-c2ccccc2)nc1CCc1ccc(/C=C/C=C/C=O)cc1
Solvent: C1CCNCC1
Solvent: CC(=O)O
Product: Cc1oc(-c2ccccc2)nc1CCc1ccc(/C=C/C=C/C=C2OC(=O)NC2=O)cc1

Procedure:
A mixture of (E,E)-5-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethyl]phenyl]-2,4-pentadien-1-al (2.3 g), 2,4-oxazolidinedione (2.0 g), piperidine (0.596 g) and acetic acid (50 ml) was refluxed under heating conditions for 15 hours. The reaction mixture was concentrated; water was added to the residue, followed by acidification with 2N HCl and subsequent extraction with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and then concentrated. The residue was subjected to silica gel chromatography to yield 5-[(E,E)-5-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethyl]phenyl]-2,4pentadienylidene]-2,4-oxazolidinedione [mixture of the (E)- and (Z)-configurations](1.0 g, 33%) from the fraction eluted with chloroform-ethyl acetate (9:1, v/v), which was then recrystallized from chloroform-methanol to yield light yellow prisms having a melting point of 208°-210° C.
Reaction SMILES: [Cl:1][C:2]1[C:7]([NH:8][S:9]([CH:12]2[CH2:14][CH2:13]2)(=[O:11])=[O:10])=[CH:6][C:5]([N:15]=C(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:4][N:3]=1.Cl>C1COCC1>[NH2:15][C:5]1[CH:6]=[C:7]([NH:8][S:9]([CH:12]2[CH2:14][CH2:13]2)(=[O:11])=[O:10])[C:2]([Cl:1])=[N:3][CH:4]=1
Reactant: O=S(=O)(Nc1cc(N=C(c2ccccc2)c2ccccc2)cnc1Cl)C1CC1
Agent: Cl
Solvent: C1CCOC1
Product: Nc1cnc(Cl)c(NS(=O)(=O)C2CC2)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of N-(2-chloro-5-(diphenylmethyleneamino)pyridin-3-yl)cyclopropanesulfonamide (0.300 g, 0.728 mmol) in THF (5 mL) was added hydrochloric acid. In (1.092 mL, 1.092 mmol). The reaction was stirred at rt in closed system. After 30 min, LC/MS showed no sign of starting materials with desired product mass as the major peak. The reaction mixture was partitioned between EtOAc and sat. NaHCO3. The aqueous layer was extracted with more EtOAc (2×10 mL). The combined organic layer were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 3% MeOH in DCM) to afford the desired product as a yellow solid (170 mg). MS (ESI pos. ion) m/z: 248.0. 1H NMR (300 MHz, CDCL3) δ ppm 1.04 (d, J=6.58 Hz, 2H) 1.13-1.32 (m, 2H) 2.51 (t, J=4.60 Hz, 1H) 3.85 (br. s., 2H) 6.63 (br. s., 1H) 7.35 (s, 1H) 7.68 (s, 1H).
Reaction SMILES: [CH3:1][C:2]([CH3:20])([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][O:15]1)[C:3](OCC)=[O:4].[H-].C([Al+]CC(C)C)C(C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>CCOCC>[CH3:1][C:2]([CH3:20])([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][O:15]1)[CH2:3][OH:4]
Reactant: CCOC(=O)C(C)(C)CCCCCOC1CCCCO1
Agent: CC(C)C[Al+]CC(C)C
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [H-]
Solvent: CCOCC
Product: CC(C)(CO)CCCCCOC1CCCCO1

Procedure:
A solution of ethyl 2,2-dimethyl-7-(tetrahydro-2H-pyran-2-yloxy)heptanoate (example 285, step b) (2.22 g) in dry ether (22 mL) at 0° C. under nitrogen, was treated dropwise over 5 minutes with diisobutylaluminium hydride (1M in toluene, 17.1 mL). After 1 hour at 0° C. the reaction mixture was treated cautiously with aqueous potassium sodium tartrate, diluted with ether and the resultant mixture was stirred vigorously for 1.5 hours. The phases were separated and the aqueous phase was extracted with ether (×2). The combined organic phase was washed with water and brine, dried over magnesium sulfate, filtered and evaporated. Purification was by silica gel chromatography eluting with 0 to 50% ethyl acetate in cyclohexane to afford the subtitled compound as a colourless oil. Yield 1.83 g.
Reaction SMILES: [O:1]1[C:5]2[C:6]([C:10]([NH2:12])=O)=[CH:7][CH:8]=[CH:9][C:4]=2[CH2:3][CH2:2]1.[BH4-].[Na+].II.CO>C1COCC1>[O:1]1[C:5]2[C:6]([CH2:10][NH2:12])=[CH:7][CH:8]=[CH:9][C:4]=2[CH2:3][CH2:2]1
Reactant: NC(=O)c1cccc2c1OCC2
Agent: II
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: NCc1cccc2c1OCC2
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 20.1 %

Procedure:
At 0° C., a solution of 2,3-dihydrobenzofuran-7-carboxylic acid amide (5.2 g, 31 mmol) in THF (100 ml) was added drop wise to a suspension of sodium borohydride in THF. The mixture was stirred for 20 min at 0° C. A solution of iodine (4.1 g, 16 mmol) in THF (100 ml) was added drop wise. After the addition was finished, the reaction mixture was heated for 16 hours to reflux. It was cooled to room temperature. Methanol (260 ml) was added drop wise. The solvent was removed in vacuo. The residue was dissolved in a 20% aqueous solution of sodium hydroxide (200 ml) and tert-butyl methyl ether (200 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (90 g), using DCM/methanol/25% aqueous ammonia (100:10:1) as eluent to give 0.93 g of ((2,3-dihydrobenzofuran-7-yl)methyl)amine
Reaction SMILES: [C:1]([N:3]=[C:4]([NH2:6])[NH2:5])#[N:2].[OH:7][CH:8]([CH3:12])[C:9](=O)[CH3:10].Cl>>[NH:3]([C:1]1[O:7][C:8]([CH3:12])=[C:9]([CH3:10])[N:2]=1)[C:4]([NH2:6])=[NH:5]
Reactant: CC(=O)C(C)O
Reactant: N#CN=C(N)N
Agent: Cl
Product: Cc1nc(NC(=N)N)oc1C

Procedure:
reacting any dicyanodiamide obtained in step (b) with 3-hydroxy-2-butanone in a non-aqueous, alcoholic hydrochloric acid medium to form 2-guanidino-4,5-dimethyloxazole;
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C@@H:15]([C:17]([OH:19])=[O:18])[NH2:16])=[CH:6][CH:5]=1)([O-])=O.O.[ClH:21]>C(O)C.[Pd]>[ClH:21].[ClH:21].[ClH:21].[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C@@H:15]([C:17]([OH:19])=[O:18])[NH2:16])=[CH:8][CH:9]=1
Reactant: N[C@@H](CCCCNc1ccc([N+](=O)[O-])cc1)C(=O)O
Agent: [Pd]
Agent: Cl
Solvent: O
Solvent: CCO
Product: Nc1ccc(NCCCC[C@H](N)C(=O)O)cc1
Reaction time: 1 h
Yield: 99 %

Procedure:
2 g (7.48 mmol) of Nε-(4-nitrophenyl)-L-lysine are dissolved in 30 ml of ethanol, 9 ml of water and 5.2 ml (3.5 eq) of 5N hydrochloric acid in a 250 ml glass reactor (Paar apparatus). 2 g of palladium-on-charcoal with a moisture content of 50% and an active content of 10% are then introduced. The mixture is hydrogenated under a pressure of approximately 2.76×105 Pa for 1 hour and at a temperature of 10° C. After filtering through celite, the filtrate is evaporated. The purplish oily residue is taken up in ethanol and precipitated from a large volume of acetone with stirring. After filtration, 2.6 g of a white crystalline powder are obtained, i.e. a final yield of 99%.
Reaction SMILES: C[Mg]Cl.[CH2:4]([O:11][C@@H:12]([CH3:33])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C@@H:19]([OH:32])[CH2:20]OS(C1C=CC(C)=CC=1)(=O)=O)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[Cl-].[NH4+].[CH2:36](OCC)C>O1CCCC1.CCCCCC.C(OCC)(=O)C>[CH2:4]([O:11][C@H:12]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C@@H:19]([OH:32])[CH2:20][CH3:36])[CH3:33])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: CCOCC
Reactant: Cc1ccc(S(=O)(=O)OC[C@H](O)CCCCCC[C@H](C)OCc2ccccc2)cc1
Agent: C[Mg]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CC[C@H](O)CCCCCC[C@H](C)OCc1ccccc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 90 %

Procedure:
To 11.8 ml of a commercially available solution of 20% methyl magnesium chloride (31.4 mmol) in tetrahydrofuran were added 20 ml abs. tetrahydrofuran. The solution was cooled to −78° C., and 595 mg (3.14 mmol) copper-I-iodide were added. After stirring for 15 min, a solution of 4.55 g (10.5 mmol) (2R,9S)-9-benzyloxy-1(p-tolylsulfonyloxy)-decane-2-ol in 10 ml abs. tetrahydrofuran was added over a period of 2 h. The solution was warmed to −30° C. and stirred for another hour. Subsequently, 150 ml saturated aqueous ammonium chloride and 50 ml diethyl ether were added at 0° C. The aqueous layer was extracted three times with 150 ml ethyl acetate. The combined organic layers were dried over magnesium sulphate and concentrated in vacuo. Flash chromatography (16% ethyl acetate in hexane) furnished 2.6 g (9.4 mmol, 90%) (2S,9S)-2-benzyloxyundecane-9-ol
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S([O:12][CH2:13][Si:14]([CH3:17])([CH3:16])[CH3:15])(=O)=O.[F:20][C:21]([N+:27]([O-:29])=[O:28])([N+:24]([O-:26])=[O:25])[CH2:22]O.C(Cl)(Cl)(Cl)Cl>C(Cl)Cl>[F:20][C:21]([N+:27]([O-:29])=[O:28])([N+:24]([O-:26])=[O:25])[CH2:22][O:12][CH2:13][Si:14]([CH3:15])([CH3:16])[CH3:17]
Reactant: C[Si](C)(C)COS(=O)(=O)C(F)(F)F
Reactant: O=[N+]([O-])C(F)(CO)[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClCCl
Product: C[Si](C)(C)COCC(F)([N+](=O)[O-])[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 16 h
Yield: 43.9 %

Procedure:
Potassium carbonate (6 g) was added to a solution of 3.5 g (0.0148 mol) of trimethylsilylmethyl trifluoromethanesulfonate and 2.3 g of 2-fluoro-2,2-dinitroethanol in 5 ml of methylene chloride, and the mixture was stirred for 16 hrs. This suspension was added with stirring to a mixture of 30 ml of ice water and 30 ml of carbon tetrachloride. The carbon tetrachloride layer was washed with 10 ml of water, dried over magnesium sulfate, and distilled to give 1.56 g (45%) of trimethylsilylmethyl 2-fluoro-2,2-dinitroethyl ether, bp 52° (0.75 mm).