Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]=[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19](=O)[CH3:20])[N:14]=1)[CH3:12].[CH2:22]([O:25][C:26]1[C:32]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:31][C:29]([NH2:30])=[CH:28][C:27]=1[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:23][CH3:24]>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]=[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19](=[N:30][C:29]2[CH:28]=[C:27]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:26]([O:25][CH2:22][CH2:23][CH3:24])=[C:32]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH:31]=2)[CH3:20])[N:14]=1)[CH3:12]
Reactant: CCCOc1c(-c2ccccc2)cc(N)cc1-c1ccccc1
Reactant: CC(=O)c1cccc(C(C)=Nc2c(C)cc(C)cc2C)n1
Solvent: Cc1ccccc1
Product: CCCOc1c(-c2ccccc2)cc(N=C(C)c2cccc(C(C)=Nc3c(C)cc(C)cc3C)n2)cc1-c1ccccc1
Reaction time: 24 h

Procedure:
2-[1-(2,4,6-trimethylphenylimino)ethyl]-6-acetylpyridine (387 mg, 1.38 mmol) and 4-propoxy-3,5-diphenylaniline (440 mg, 1.45 mmol) were dissolved in 50 ml of toluene. To this solution, 4 Å molecular sieves were added. After standing for 1 day the mixture was filtered. The solvent was removed in vacuo. The residue was crystallised from cold ethanol. The product was isolated as a yellow treacle (700 mg) and used as such.
Reaction SMILES: [CH2:1]([CH:16]1[CH2:21][CH2:20][CH2:19][C:18](=O)[CH2:17]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].Cl.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[NH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>ClCCl>[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:18]2([C:35]3[CH:36]=[CH:37][C:32]([NH2:31])=[CH:33][CH:34]=3)[CH2:19][CH2:20][CH2:21][CH:16]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:17]2)=[CH:27][CH:26]=1
Reactant: Nc1ccccc1
Reactant: CCCCCCCCCCCCCCCC1CCCC(=O)C1
Agent: Cl
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCC1CCCC(c2ccc(N)cc2)(c2ccc(N)cc2)C1
Temperature: 140 °C

Procedure:
A 100 mL single necked flask fitted with a magnetic stirrer and a reflux condenser was charged with a 10.0 g (32 mmol) of 3-pentadecylcyclohexanone, 8.4 g (65 mmol) aniline hydrochloride and 12.05 g (130 mmol) of aniline. The resulting mixture was refluxed at 140° C. for 10 hours under positive pressure of nitrogen. The reaction mixture was cooled to room temperature, diluted with dichloromethane, and washed with aqueous sodium hydroxide solution and water and dried over sodium sulfate. Solvent was distilled off and excess aniline removed under vacuum. The desired 1,1-bis(4-aminophenyl)-3-pentadecylcyclohexan was obtained in a yield of 5.4 g (35% of theoretical). M.p. 107° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7](CO)=[CH:6][C:5]=1[O:12][C:13](=[O:15])[CH3:14].[OH:17][C:18]1[C:23]([I:24])=[CH:22][C:21]([C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:26])=[CH:20][C:19]=1[I:33].[C:34]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([CH2:34][O:17][C:18]2[C:19]([I:33])=[CH:20][C:21]([C:25](=[O:26])[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:22][C:23]=2[I:24])[CH:7]=[CH:6][C:5]=1[O:12][C:13](=[O:15])[CH3:14]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: COC(=O)c1ccc(CO)cc1OC(C)=O
Reactant: O=C(c1ccccc1)c1cc(I)c(O)c(I)c1
Agent: CCOC(=O)/N=N/C(=O)OCC
Solvent: c1ccccc1
Product: COC(=O)c1cc(COc2c(I)cc(C(=O)c3ccccc3)cc2I)ccc1OC(C)=O
Yield: 54.5 %

Procedure:
The title compound was prepared according to the procedure in Example 1, step 5 using 2-acetoxy-4-(hydroxymethyl) benzoic acid methyl ester (0.109 g, 0.484 mmol), (4-hydroxy-3,5-diiodo-phenyl)-phenyl-methanone (0.218 g, 0.484 mmol), triphenylphosphine (0.140 g, 0.533 mmol) and diethylazodicarboxylate (83.5 μL, 0.533 mmol) in benzene (4.84 mL). Purification on Biotage KP-Sil eluting with a 10, 15 & 20% EtOAc/pet. ether gave 0.173 g (54%) of the title compound as a white solid, mp 132-135° C. 1H NMR (DMSO-d6) δ 2.30 (s, 3H), 3.83 (s, 3H), 5.09 (s, 2H), 7.35 (d, 1H), 7.58 (t, 2H), 7.69-7.75 (m, 3H), 7.92 (dd, 1H), 8.13 (d, 2H), 8.19 (d, 1 H). IR (KBr) 2950, 1760, 1220, 1660 and 1275 cm-1. mass spectrum (+FAB) m/z 657 (M+H), 679 (M+Na).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20](Cl)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][N:25]1[CH:30]=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][C:26]1=[O:40]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20]([C:28]4[CH:29]=[CH:30][N:25]([CH3:24])[C:26](=[O:40])[CH:27]=4)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cn1ccc(B2OC(C)(C)C(C)(C)O2)cc1=O
Reactant: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(Cl)ncc3O2)CC1
Product: Cn1ccc(-c2cc3c(cn2)OC(C2CCN(C(=O)OC(C)(C)C)CC2)C3)cc1=O

Procedure:
The title compound is prepared from 4-(5-chloro-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester and 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one following a procedure analogous to that described in Example 28. LC (method 10): tR=1.61 min; Mass spectrum (ESI+): m/z=412 [M+H]+.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([C:18]#[N:19])=[CH:13][CH:14]=2)[CH:9]1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)(C)(C)C.Cl>ClCCl.C(O)(C)C>[ClH:27].[NH2:7][CH:8]1[CH:9]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=2)[C:10]2[CH:11]=[C:12]([C:18]#[N:19])[CH:13]=[CH:14][C:15]=2[CH2:16][CH2:17]1
Reactant: CC(C)(C)OC(=O)NC1CCc2ccc(C#N)cc2C1Cc1ccc(Cl)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CC(C)O
Product: N#Cc1ccc2c(c1)C(Cc1ccc(Cl)cc1)C(N)CC2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Tert-butyl[1-(4-chlorobenzyl)-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (15 mg, 0.038 mmol) was dissolved in dichloromethane (1.5 mL) and 5 M hydrochloric acid in isopropanol (0.3 mL) was added. The reaction mixture was stirred for 3 h at room temperature. The solvent and the excess hydrochloric acid were evaporated in vacuo. Yield: 11 mg (0.033 mmol, 87%, colorless solid).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH2:8])[C:3]=1[I:9].[CH:10]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][CH:13]=[C:12]([OH:19])[CH:11]=1.C(N(C(C)C)CC)(C)C.CN1CCCC1=O>O>[I:9][C:3]1[C:4]([NH2:8])=[N:5][CH:6]=[CH:7][C:2]=1[O:19][C:12]1[CH:11]=[CH:10][C:15]([N+:16]([O-:18])=[O:17])=[CH:14][CH:13]=1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: Nc1nccc(Cl)c1I
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN1CCCC1=O
Product: Nc1nccc(Oc2ccc([N+](=O)[O-])cc2)c1I
Yield: 38.5 %

Procedure:
4-Chloro-3-iodo-2-pyridinamine (1.0 g), p-nitrophenol (1.1 g), diisopropylethylamine (1.0 ml) and N-methyl-2-pyrrolidone (2 ml) were stirred at 170° C. for 17 hours. After returning the reaction solution to room temperature, water was added and extraction was performed with ethyl acetate. NH type silica gel was added to the extract, the solvent was distilled off under reduced pressure, and the reaction product was adsorbed onto the silica gel. The silica gel was charged into a dry column packed with NH type silica gel, and column purification was performed (hexane:ethyl acetate=3:1). The solvent was distilled off under reduced pressure, and then ethyl acetate and hexane were added to the residue for solidification to obtain 540 mg of light yellow crystals.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([CH2:17][N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[CH:16][C:11]=3[N:10]=[C:9]2[NH2:24])[CH:5]=[CH:6][CH:7]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:49][C:50]([F:61])([F:60])[C:51]1[CH:52]=[C:53]([CH:57]=[CH:58][CH:59]=1)[C:54](O)=[O:55].O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([CH2:17][N:18]4[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]4)=[CH:16][C:11]=3[N:10]=[C:9]2[NH:24][C:54](=[O:55])[C:53]2[CH:57]=[CH:58][CH:59]=[C:51]([C:50]([F:49])([F:60])[F:61])[CH:52]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1cccc(C(F)(F)F)c1
Reactant: Nc1nc2cc(CN3CCCCC3)ccc2n1-c1cccc(F)c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Solvent: O
Product: O=C(Nc1nc2cc(CN3CCCCC3)ccc2n1-c1cccc(F)c1)c1cccc(C(F)(F)F)c1
Reaction time: 24 h
Yield: 13 %

Procedure:
N-[1-(3-fluorophenyl)-5-piperidino-1-ylmethyl-1H-benzoimidazol-2-yl]-3-trifluoromethyl-benzamide: 500 mg 1-(3-fluorophenyl)-5-piperidin-1-ylmethyl-1H-benzoimidazol-2-ylamine (1.54 mmol, 1.0 equiv) was combined in a flask with 877 mg O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 2.32 mmol, 1.5 equiv), 440 mg 3-trifluoromethylbenzoic acid (2.32 mmol, 1.5 equiv) and 312 mg 1-hydroxybenzotriazole hydrate (HOBT, 2.32 mmol, 1.5 equiv) followed by the addition of 12 mL DMF and 254 μL N-methylmorpholine (NMM, 2.32 mmol, 1.5 equiv). The solution was allowed to stir for 24 h and then diluted with sat. Na2HCO3. The solution was extracted (2×10% MeOH/CH2Cl2), washed (1×brine), dried (NaSO4) and concentrated under reduced pressure. Purification by flash chromatography (SiO2, 5% MeOH/CH2Cl2) gave 0.2 g of the product as a tan solid (0.2 mmol). 1H NMR (DMSO-d6, 400 MHz) 13.0 (s, 1 H), 8.35 (s, 1 H), 8.30 (d, J=7.6 Hz, 1 H), 7.88 (d, J=7.6 Hz, 1 H), 7.72 (m, 3 H), 7.62 (m, 2 H), 7.47 (t, J=7.6 Hz, 1 H), 7.22 (broad s, 2 H), 3.55 (s, 2 H), 2.38 (broad s, 4 H), 1.5 (m, 6 H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N+:10]=2[O-])=[CH:5][CH:4]=1.C(O)(C)C>[Pd].C1CCCCC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH2:20][CH2:21][CH:22]([C:26]([OH:28])=[O:27])[CH2:23]4)=[CH:18][CH:17]=3)[CH:12]=[CH:11][N:10]=2)=[CH:30][CH:31]=1
Reactant: COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)cc[n+]2[O-])cc1
Agent: [Pd]
Solvent: CC(C)O
Solvent: C1=CCCCC1
Product: COc1ccc(CNc2cc(Oc3ccc4c(c3)CC(C(=O)O)CC4)ccn2)cc1
Temperature: 85 °C

Procedure:
A mixture of 7-({2-[(4-methoxybenzyl)amino]-1-oxidopyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (21.1 g, 0.0502 mol), cyclohexene (100 mL, 0.9 mol) and Pd (10% on Carbon, 4.5 g) in isopropyl alcohol (400 mL, 5 mol) was heated at 85° C. overnight. Additional catalyst (2.5 g) and cyclohexene (30 mL) were added. The mixture was heated at 90° C. overnight and then filtered. The filtrate was concentrated to give 7-({2-[(4-methoxybenzyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid which was used in the next step without purification. LCMS ES+ 405.7
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:24])[C:9]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=1[N:18]1[C:22]([CH3:23])=[CH:21][N:20]=[CH:19]1.[CH2:25]=[O:26]>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:24])[C:9]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=1[N:18]1[C:22]([CH3:23])=[CH:21][N:20]=[C:19]1[CH2:25][OH:26]
Reactant: C=O
Reactant: Cc1cncn1-c1ccc([N+](=O)[O-])cc1C(=O)c1ccccc1Cl
Solvent: Cc1ccccc1C
Product: Cc1cnc(CO)n1-c1ccc([N+](=O)[O-])cc1C(=O)c1ccccc1Cl

Procedure:
In the manner given in Example 1, 2'-chloro-5-nitro(5-methylimidazol-1-yl)benzophenone is heated in a bomb with paraformaldehyde in xylene to 140° C. to give 2'-chloro-5-nitro-2-[5-methyl-2-(hydroxymethyl)imidazol-1-yl]benzophenone.
Reaction SMILES: [NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([OH:12])=O)[CH2:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.[NH:20]1[CH2:34][CH2:33][CH2:32][C@H:21]1[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]>>[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([N:20]1[CH2:34][CH2:33][CH2:32][C@H:21]1[C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])=[O:12])[CH2:3][CH:4]1[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]1
Reactant: CC(C)(C)OC(=O)N[C@H](CC1CCCCC1)C(=O)O
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1
Product: CC(C)(C)OC(=O)N[C@H](CC1CCCCC1)C(=O)N1CCC[C@H]1C(=O)OCc1ccccc1

Procedure:
Boc-D-Cha-Pro-OBzl was prepared according a similar manner as described in example 1 using Boc-D-Cha and Pro-OBzl.
Reaction SMILES: C(N(CC)CC)C.CN1CCN(C)C1=O.Br.[NH2:17][CH2:18][CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[CH:29][C:30](=[O:33])[NH:31][N:32]=2)=[CH:23][CH:22]=1.Cl[CH2:35][CH2:36][S:37](Cl)(=[O:39])=[O:38]>O1CCCC1>[CH:36]([S:37]([NH:17][CH2:18][CH2:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[CH:28]=[CH:29][C:30](=[O:33])[NH:31][N:32]=2)=[CH:25][CH:26]=1)(=[O:39])=[O:38])=[CH2:35]
Reactant: O=S(=O)(Cl)CCCl
Reactant: NCCCc1ccc(-c2ccc(=O)[nH]n2)cc1
Agent: Br
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CN1CCN(C)C1=O
Product: C=CS(=O)(=O)NCCCc1ccc(-c2ccc(=O)[nH]n2)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 37.3 %

Procedure:
3.54 g of triethylamine was added to a 1,3-dimethyl-2-imidazolidinone suspension (35 ml) containing 3.10 g of 6-[4-(3-aminopropyl)phenyl]pyridazin-3(2H)-one hydrobromide. Then, a tetrahydrofuran solution (15 ml) containing 1.95 g of chloroethylsulfonyl chloride was added to the mixture, and the resulting mixture was stirred at room temperature for 5 hours. The reaction mixture was poured into ice water and extracted with chloroform. After the chloroform layer was washed with water and dried, the solvent was removed. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol (10: 1)) to obtain 1.19 g of 6-[4-(3-vinylsulfonylaminopropyl)phenyl]-pyridazin-3(2H)-one.
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]1[CH:11]=[CH:10][C:8](=[O:9])[NH:7][C:5]1=[O:6].Br[CH2:13][CH2:14][CH2:15][CH2:16][CH:17]=[CH2:18].O>CS(C)=O>[CH:13]([N:7]1[C:8](=[O:9])[CH:10]=[CH:11][N:4]([CH3:3])[C:5]1=[O:6])=[CH:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: C=CCCCCBr
Reactant: Cn1ccc(=O)[nH]c1=O
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCCCC=Cn1c(=O)ccn(C)c1=O
Reaction time: 0.25 h
Yield: 71786.3 %

Procedure:
This example illustrates a synthesis of 3-(5,6-Oxidohexyl)-1-methyluracil (inventive compound no. 1808). Sodium hydride (86 mg, 3.6 mmol) was added to a stirring solution of 1-methyluracil (500 mg, 4 mmol) in dimethyl sulfoxide (25 mL). After 15 minutes, 6-bromo-1-hexene (647 mg, 4 mmol) was added and the mixture stirred further for 20 hours. The reaction mixture was then poured into water (50 mL) and extracted with 20% ethanol/dichloromethane (3×50 mL). The combined organic layers were washed with aqueous saturated salt solution (20 mL) and dried over sodium sulfate. The solvent was evaporated under vacuum to give a residue which was purified by chromatography with silica and ethyl acetate to yield 598 g (72% yield) of 3-hexenyl-1-methyluracil (inventive compound no. 1800).
Reaction SMILES: [CH3:1][C:2]1([C:15]([O:17][CH3:18])=[O:16])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[O:12][CH3:13])[C:3]1=O.C(OCC)(=O)C.O>FC(F)(F)C(O)=O>[CH3:1][C:2]1([C:15]([O:17][CH3:18])=[O:16])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[O:12][CH3:13])[CH2:3]1
Reactant: COC(=O)C1(C)CCc2c(OC)cccc2C1=O
Solvent: CCOC(C)=O
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)C1(C)CCc2c(cccc2OC)C1
Temperature: 25 °C
Reaction time: 6 h
Yield: 211.9 %

Procedure:
To a solution of 2-methyl-2-methoxycarbonyl-5-methoxy-1-oxo-1,2,3,4-tetrahydronaphthalene (2.0 g) in trifluoroacetic acid (20 ml) was added triethyls4lane (2.0 ml) at room temperature. After being stirred for 6 hours at room temperature, the solution was poured into a mixture of ethyl acetate and water. The organic layer was washed with 1N-HCl solution, sat. NaHCO3, and brine, dried over MgSO4, and evaporated in vacuo. The residue was purified by chromatography on silica gel to afford 2-methyl-2-methoxycarbonyl-5-methoxy-1,2,3,4-tetrahydronaphthalene (4.0 g).
Reaction SMILES: C(N(CC[OH:13])C1C=CC=C(C)C=1)C.[S:14]([OH:18])([OH:17])(=[O:16])=[O:15].[NH2:19][C:20]1[CH:31]=[CH:30][C:23]([N:24]([CH2:28][CH3:29])[CH2:25][CH2:26][OH:27])=[CH:22][C:21]=1[CH3:32].S(=O)(=O)(O)O>>[S:14]([OH:18])([OH:17])(=[O:16])=[O:15].[CH2:28]([N:24]([CH2:25][CH2:26][OH:27])[C:23]1[CH:30]=[CH:31][C:20]([N:19]=[O:13])=[C:21]([CH3:32])[CH:22]=1)[CH3:29]
Reactant: CCN(CCO)c1ccc(N)c(C)c1
Reactant: CCN(CCO)c1cccc(C)c1
Agent: O=S(=O)(O)O
Product: CCN(CCO)c1ccc(N=O)c(C)c1

Procedure:
A process for producing 4-amino-3-methyl-N-ethyl-N-(β-hydroxyethyl)aniline sulfate which comprises nitrosating N-ethyl-N-(β-hydroxyethyl)-m-toluidine with an alkyl nitrite in an aqueous alcohol solution containing 30-90% by volume of the alcohol and about 0.5 to about 1 mole of sulfuric acid per mole of the N-ethyl-N-(β-hydroxyethyl)-m-toluidine to form N-ethyl-N-(β-hydroxyethyl)-3-methyl-4-nitrosoaniline sulfate, and catalytically hydrogenating the N-ethyl-N-(β-hydroxyethyl)-3-methyl-4-nitrosoaniline sulfate.
Reaction SMILES: [F:1][C@@H:2]1[C@@H:6]([CH2:7][OH:8])[O:5][C@@H:4]([N:9]2[CH:16]=[CH:15][C:13](=O)[NH:12][C:10]2=[O:11])[CH2:3]1.[C:17]([O:20]C(=O)C)(=O)[CH3:18].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:25]>N1C=CC=CC=1>[C:17]([O:8][CH2:7][C@H:6]1[O:5][C@@H:4]([N:9]2[CH:16]=[CH:15][C:13](=[S:25])[NH:12][C:10]2=[O:11])[CH2:3][C@@H:2]1[F:1])(=[O:20])[CH3:18]
Reactant: O=c1ccn([C@H]2C[C@H](F)[C@@H](CO)O2)c(=O)[nH]1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)OC[C@H]1O[C@@H](n2ccc(=S)[nH]c2=O)C[C@@H]1F
Reaction time: 8 h

Procedure:
1-(2,3-Dideoxy-3-fluoro-β-D-ribofuranosyl)-uracil (1.3 mmoles) is dissolved in 45 mL of pyridine and treated with 1.1 mL of acetic anhydride. The reaction mixture is allowed to stand overnight at room temperature. The solution is concentrated, the residue dissolved in toluene and evaporated to dryness once more. The process is repeated several times. The residue, finally obtained, is dissolved in 80 mL of pyridine, mixed with 3.9 mmoles of phosphorus pentasulfide and refluxed for 6 hours. After this reaction time, a further 1.3 mmoles of phosphorus pentasulfide are added (J. J. Fox et al., J. Am. Chem. Soc. 1959, 81, 178; G. Kowollik et al., J. Prakt. Chem. 1973, 315, 895) and the mixture is refluxed for 6 hours. The reaction mixture is allowed to cool and the liquid portion is separated is separated from the remainder and evaporated to dryness under vacuum. The resulting residue is purified by column chromatography on a silicage sold by Merck, Darmstadt under the trade name Kieselgel 40, with chloroform as eluting agent. 1-(5-O-Acetyl-2,3-dideoxy-3-fluoro-β-D-ribofuranosyl)-4-thiouracil is isolated from the appropriate fractions and, after recrystallization from 90% ethanol, is obtained in a yield of 97 mg and has a melting point of 140°-140.5° C. This compound (15 mg, 0.06 mmoles) is dissolved in 2 mL of methanol and mixed at 0'C with 2 mL of ammonia-saturated methanol. After 24 hours, the solution is evaporated to dryness. The compound is obtained as a glass.
Reaction SMILES: C(OC([C:6]1([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[S:18][C:9]23[CH:17]=[CH:16][CH:15]=[CH:14][C:10]2=[N:11][CH2:12][CH2:13][CH:8]3[CH2:7]1)=O)C.[OH-:26].[Na+].[CH3:28][OH:29]>C(Cl)(Cl)Cl>[C:22]([O:21][C:19]([CH:6]1[S:18][C:9]23[CH:17]=[CH:16][CH:15]=[CH:14][C:10]2=[N:11][CH2:12][CH2:13][CH:8]3[CH:7]1[C:28]([OH:29])=[O:26])=[O:20])([CH3:25])([CH3:23])[CH3:24]
Reactant: CO
Reactant: [OH-]
Reactant: CCOC(=O)C1(C(=O)OC(C)(C)C)CC2CCN=C3C=CC=CC32S1
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CC(C)(C)OC(=O)C1SC23C=CC=CC2=NCCC3C1C(=O)O
Yield: 75 %

Procedure:
In a mixed solvent of 30 ml of methanol and 20 ml of chloroform was dissolved 6 g of 2-tert-butoxycarbonyl-1,2,3,4-tetrahydrobenzo[b]thieno[2,3-c]pyridine-carboxylic acid ethyl ester and 4 ml of an aqueous solution of 5N sodium hydroxide was further added thereto, and then the solution was refluxed for 5 hours. The solvents were distilled off under reduced pressure and 300 ml of 5% citric acid and 300 ml of chloroform were added to the residue. The chloroform layer was washed with a saturated aqueous sodium chloride solution and then dried by sodium sulfate. After distilling off chloroform under reduced pressure, the residue formed was recrystallized from a mixture of chloroform and hexane to provide 4.15 g (yield of 75%) of 2-tert-butoxycarbonyl-1,2,3,4-tetrahydrobenzo[b]thieno[2,3-c]pyridine-3-carboxylic acid.
Reaction SMILES: [F:1][CH:2]([F:36])[O:3][C:4]1[CH:5]=[C:6]([CH:14]([C:22]2[CH:23]=[N:24][C:25]([O:28][C:29]3[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=3)=[CH:26][CH:27]=2)[CH2:15][C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH:11]([F:13])[F:12].CCN(CC)CC.[CH3:44][S:45](Cl)(=[O:47])=[O:46]>C(Cl)Cl>[F:36][CH:2]([F:1])[O:3][C:4]1[CH:5]=[C:6]([CH:14]([C:22]2[CH:23]=[N:24][C:25]([O:28][C:29]3[CH:30]=[CH:31][C:32]([NH:35][S:45]([CH3:44])(=[O:47])=[O:46])=[CH:33][CH:34]=3)=[CH:26][CH:27]=2)[CH2:15][C:16]2[CH:17]=[CH:18][N:19]=[CH:20][CH:21]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH:11]([F:13])[F:12]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1ccc(Oc2ccc(C(Cc3ccncc3)c3ccc(OC(F)F)c(OC(F)F)c3)cn2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)Nc1ccc(Oc2ccc(C(Cc3ccncc3)c3ccc(OC(F)F)c(OC(F)F)c3)cn2)cc1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 51 %

Procedure:
To a 0° C. solution of amine from Step 1 above (200 mg, 0.4 mmol) in 6 mL of CH2Cl2 was added 0.28 mL (2.0 mmol) of Et3N followed by 0.11 mL (1.4 mmol) of methylsulfonyl chloride. The solution was stirred at 0° C. for 1.5 h, quenched with water and diluted with CH2Cl2. The organic layer was washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was dissolved in 10 mL of a 1:1:1 mixture of THF:MeOH: 1 N K2CO3, stirred for 3.5 h at room temperature, quenched with a saturated aqueous NH4Cl solution and diluted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (100% ethyl acetate) to afford the methyl sulfonamide as a foam (114 mg, 51%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:10]=[CH:9][NH:8][N:7]=1)=[O:5])[CH3:2].I[CH:12]([CH3:14])[CH3:13].CC[O-].[Na+].CC(O)=O>C1COCC1.O>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[CH:9][N:8]([CH:12]([CH3:14])[CH3:13])[N:7]=1)=[O:5])[CH3:2]
Reactant: CC(C)I
Reactant: CCOC(=O)c1cc[nH]n1
Agent: CC[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)c1ccn(C(C)C)n1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 95.5 %

Procedure:
To 1H-pyrazole-3-carboxylic acid ethyl ester (23.1 g, 165 mmol) in THF (330 mL) was added 2-iodopropane (33.0 mL, 330 mmol) followed by NaOEt (21% in EtOH, 65.0 mL, 174 mmol). This solution was then heated to reflux for 16 h. The reaction was then allowed to cool to room temperature. AcOH (10.5 mL, 183 mmol) was added and the reaction was stirred for 5 min. H2O (400 mL) was added to the solution, and this mixture was extracted with EtOAc (3×150 mL). The combined organic was washed with sat. aq. NaHCO3, then brine. The organic was dried over MgSO4, filtered, and concentrated to give the product (28.70 g, 96%) as a brown oil containing a 98:2 mixture of regioisomers by 1H NMR.