Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](Cl)=[O:7])#[CH:2].[CH3:12][S-:13].[Na+]>ClCCl>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([S:13][CH3:12])=[O:7])#[CH:2]
Reactant: C#Cc1cccc(C(=O)Cl)c1
Reactant: C[S-]
Agent: [Na+]
Solvent: ClCCl
Product: C#Cc1cccc(C(=O)SC)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Air in a 20 ml Schlenk tube was replaced by Ar gas and 1.02 g (7 mmol) of m-ethynylbenzoic acid and 5 g (42 mmol) of thionyl chloride were added to the tube and the mixture was stirred at 50° C. for 2 hours and then excess thionyl chloride was removed by distillation under reduced pressure to obtain m-ethynylbenzoyl chloride. To the m-ethynylbenzoyl chloride obtained was added 7 ml of dichloromethane and the resultant mixture was ice-cooled. Then, 515 mg (7.35 mmol) of sodium methanethiolate was added to the mixture and the mixture was stirred at room temperature for 3 hours. After completion of the stirring, dichloromethane was removed by distillation under reduced pressure and 35 ml of water was added to the resultant residue. The mixture was extracted with 35 ml of ethyl acetate and the extract was dried over magnesium sulfate and the solvent was removed by distillation under reduced pressure using an evaporator. The resultant crude reaction product was purified by column chromatography (Hexane/AcOEt=10/1) using silica gel to obtain 0.49 g of S-methyl 3-ethynyl-thiobenzoate which is a desired product as yellow solid. (Yield: 40%)
Reaction SMILES: [C:1]1([N:7]2[C:12](=[O:13])[C:11]3[S:14][CH:15]=[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:10]=3[N:9]=[CH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N[C:24]1[C:28](C2C=CC=CC=2)=CS[C:25]=1C(OC)=O.C(OCC)(OCC)OCC.C(C1CCC(N)CC1)(C)C>C(O)(=O)C>[CH:24]([CH:4]1[CH2:5][CH2:6][CH:1]([N:7]2[C:12](=[O:13])[C:11]3[S:14][CH:15]=[C:16]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:10]=3[N:9]=[CH:8]2)[CH2:2][CH2:3]1)([CH3:28])[CH3:25]
Reactant: COC(=O)c1scc(-c2ccccc2)c1N
Reactant: O=c1c2scc(-c3ccccc3)c2ncn1-c1ccccc1
Agent: CC(C)C1CCC(N)CC1
Solvent: CCOC(OCC)OCC
Solvent: CC(=O)O
Product: CC(C)C1CCC(n2cnc3c(-c4ccccc4)csc3c2=O)CC1
Yield: 58.4 %

Procedure:
In the same manner as the synthesis of Compound 1, methyl 3-amino-4-phenylthiophene-2-carboxylate (100 mg, 0.43 mmol), triethyl orthoformate (1 ml), 4-isopropylcyclohexylamine (0.148 ml, 0.90 mmol), and acetic acid (0.1 ml) were used to give 88.5 mg (0.25 mmol, 58.4% yield) of the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[NH:26][C:25](=[O:27])[O:24][N:23]=3)=[CH:12][CH:11]=2)[C:7]2[C:28]([C:32]([OH:34])=[O:33])=[CH:29][CH:30]=[CH:31][C:6]=2[N:5]=1)[CH3:2].O[CH2:36][C:37]1[O:38][C:39](=[O:43])[O:40][C:41]=1[CH3:42].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.O.CC(C)=O>[CH2:1]([O:3][C:4]1[N:8]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]3[NH:26][C:25](=[O:27])[O:24][N:23]=3)=[CH:14][CH:15]=2)[C:7]2[C:28]([C:32]([O:34][CH2:36][C:37]3[O:38][C:39](=[O:43])[O:40][C:41]=3[CH3:42])=[O:33])=[CH:29][CH:30]=[CH:31][C:6]=2[N:5]=1)[CH3:2]
Reactant: CCOc1nc2cccc(C(=O)O)c2n1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Reactant: Cc1oc(=O)oc1CO
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(=O)N(C)C
Solvent: CC(C)=O
Product: CCOc1nc2cccc(C(=O)OCc3oc(=O)oc3C)c2n1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Temperature: 10 °C
Reaction time: 3 h
Yield: 94.6 %

Procedure:
To a solution of 2-ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid (9.0 g) and 4-hydroxymethyl-5-methyl-1,3-dioxol-2-one (3.08 g) in N,N-dimethylacetamide (100 mL) were added p-toluenesulfonyl chloride (4.13 g), N,N-dimethylaminopyridine (0.48 g) and potassium carbonate (3.54 g) under ice-cooling and the mixture was stirred at about 10° C. for 3 hrs. After adjusting the pH of the mixture to about 5, the mixture was crystallized by adding water (72 mL) to give crystals as a solvate. The isolated crystals were suspended in a mixture of water (63 mL) and acetone (27 mL) and the suspension was stirred at about 35° C. for 2 hrs. After stirring under ice-cooling for 2 hrs, the crystals were collected by filtration and the crystals were washed with water (18 mL) and dried under reduced pressure at 40° C. to give the title compound (10.6 g, 95%).
Reaction SMILES: [Cl:1][C:2]1[C:14]([CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:13][CH:12]=[CH:11][C:3]=1[O:4][C@H:5]1[CH2:8][C@H:7]([CH2:9][NH2:10])[CH2:6]1.[CH2:21](N(CC)CC)C.[CH3:28][C:29]1[C:33]([C:34](Cl)=[O:35])=[C:32]([CH3:37])[O:31][N:30]=1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[C:14]([CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:13][CH:12]=[CH:11][C:3]=1[O:4][C@H:5]1[CH2:8][C@H:7]([CH2:9][N:10]([CH3:21])[C:34]([C:33]2[C:29]([CH3:28])=[N:30][O:31][C:32]=2[CH3:37])=[O:35])[CH2:6]1
Reactant: CCN(CC)CC
Reactant: Cc1noc(C)c1C(=O)Cl
Reactant: NC[C@H]1C[C@H](Oc2cccc(CN3CCCC3)c2Cl)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: Cc1noc(C)c1C(=O)N(C)C[C@H]1C[C@H](Oc2cccc(CN3CCCC3)c2Cl)C1
Product: Cl

Procedure:
Example 386, ({trans-3-[2-Chloro-3-(pyrrolidin-1-ylmethyl)phenoxy]cyclobutyl}methyl) amine (200 mg, 0.7 mmol) and triethylamine (0.1 mL, 0.7 mmol) were dissolved in CH2Cl2 (2 mL). 3,5-Dimethylisoxazole-4-carbonyl chloride (109 mg, 0.7 mmol) was added dropwise under stirring. The mixture was stirred at RT for 3 h and sat. K2CO3 was added. The mixture was stirred at RT for 20 h, dried with Na2SO4, and evaporated. The residue was purified chromatographically (silica gel 40-63 μm, 3 g, hexane/CHCl3 20:80→0:100, then CHCl3/MeOH 100:0→95:5). The residue was dissolved in ether (1 mL). 4N HCl/dioxane (0.20 mL) was added, and the reaction mixture was evaporated to dryness. The obtained crystals were washed with ether and dried in vacuo to give the title compound (170 mg, 55%) as yellow crystals. LC/MS data: 418.1 (M+H) (calculated for C22H28ClN3O3 417.94). 1H NMR-data (DMSO-d6): 10.36 (br.s, 1H, NH+); 7.87-8.40 (m, 1H, NH); 7.30-7.44 (m, 2H, Ar—H); 6.96-7.04 (m, 1H, Ar—H); 4.88-5.00 (m, 1H), 4.46-4.52 (m, 2H); 3.35-3.48 (m, 4H); 3.08-3.19 (m, 2H); 2.52-2.62 (m, 1H); 2.48 (s, 3H); 2.31-2.40 (m, 2H); 2.28 (s, 3H); 2.13-2.23 (m, 2H); 1.97-2.10 (m, 2H); 1.83-1.94 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([C:14]2([OH:24])[CH:21]3[CH2:22][CH:17]4[CH2:18][CH:19]([CH2:23][CH:15]2[CH2:16]4)[CH2:20]3)[N:9]2[CH:13]=[CH:12][N:11]=[CH:10]2)[CH:5]=[CH:6][CH:7]=1.[C:25]([OH:34])(=[O:33])[C@H:26]([C@@H:28]([C:30]([OH:32])=[O:31])[OH:29])[OH:27]>CO.C(#N)C>[C:30]([CH:28]([CH:26]([C:25]([OH:34])=[O:33])[OH:27])[OH:29])([OH:32])=[O:31].[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([C:14]2([OH:24])[CH:15]3[CH2:23][CH:19]4[CH2:18][CH:17]([CH2:22][CH:21]2[CH2:20]4)[CH2:16]3)[N:9]2[CH:13]=[CH:12][N:11]=[CH:10]2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)[C@@H](O)[C@H](O)C(=O)O
Agent: OC1(C(c2cccc(Cl)c2)n2ccnc2)C2CC3CC(C2)CC1C3
Solvent: CC#N
Solvent: CO
Product: O=C(O)C(O)C(O)C(=O)O
Temperature: 25 °C
Reaction time: 48 h

Procedure:
43.0 g (125.4 mmol) of (3-chlorophenyl)-(2-hydroxy-2-adamantyl)-(1-imidazolyl)-methane and 18.83 g (125.4 mmol) of D(-)-tartaric acid were dissolved in a mixture of 67 ml of methanol and 440 ml of acetonitrile at the boiling point. When the solution was slowly cooled to room temperature, crystallization occurred. After 2 days, the crystals were filtered off under suction and washed with acetonitrile and ether and dried for 3 hours at 98° C./3-6 mbar. 23.50 g of (3-chlorophenyl)-(2-hydroxy-2-adamantyl)-(1-imidazolyl)-methane hydrogen tartrate ([α]D : (+) 4.26° (c=1.0, CH3OH)) were obtained. This product was dissolved in a boiling mixture of 33 ml of methanol and 193 ml of acetonitrile and allowed to crystallize out at room temperature. After isolation as described above, 18.00 g of product [α]D22 : (+) 5.30° (c=1.0, CH3OH)) were obtained. These 18.00 g were recrystallized in an analogous manner from 26 ml of methanol and 151 ml of acetonitrile. 14.2 g of product [α]D22 : (+) 5.53° (c=1.0, CH3OH)) were obtained. A further recrystallization from 20 ml of methanol and 116 ml of acetonitrile gave 11.7 g of product ([α]D22 : (+) 5.90° (c=1.0, CH3OH)). Further recrystallization of this substance from 16 ml of methanol and 95 ml of acetonitrile in 9.60 g of (3-chlorophenyl)-(2-hydroxy-2-adamantyl)-(1-imidazolyl)-methane hydrogen tartrate ([α]D22 : (+) 6.18° (c=1.0, CH 3 OH)) as a pure diastereomeric salt of melting point 112°-113° C. (decomposition).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([O:14][CH3:15])[C:11]=1[O:12][CH3:13])[C:6]([OH:8])=O.ClCC(OC(=O)CCl)=O.[S:25]1[CH:29]=[CH:28][CH:27]=[CH:26]1>ClC(Cl)C>[CH3:15][O:14][C:10]1[CH:9]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:11]=1[O:12][CH3:13])[C:6]([C:26]1[S:25][CH:29]=[CH:28][CH:27]=1)=[O:8]
Reactant: c1ccsc1
Reactant: COc1cc(C(=O)O)cc(OC)c1OC
Agent: O=C(CCl)OC(=O)CCl
Solvent: CC(Cl)Cl
Product: COc1cc(C(=O)c2cccs2)cc(OC)c1OC
Temperature: 65 °C
Reaction time: 6 h
Yield: 41.5 %

Procedure:
In 50 ml of dichloroethane were dissolved 10.6 g (0.05 mole) of 3,4,5-trimethoxybenzoic acid and 9.83 g (0.0575 mole) of monochloroacetic anhydride. To the resulting solution were added 5.47 g (0.065 mole) of thiophene and 0.71 g of boron trifluoride-diethyl ether complex and the resulting mixture was then stirred at 65° C. for 6 hours. After completion of the reaction, the reaction solution was cooled and washed successively with water, 5% aqueous sodium carbonate solution and water. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain 5.77 g of 2-(3,4,5-trimethoxybenzoyl)thiophene.
Reaction SMILES: [C:1]([O-:4])(=[O:3])[CH3:2].[Na+].[CH2:6]([Si:14](Cl)(Cl)Cl)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]>CCCCCCC>[CH2:6]([Si:14]([O:4][C:1](=[O:3])[CH3:2])([O:3][C:1](=[O:4])[CH3:2])[O:3][C:1](=[O:4])[CH3:2])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCCCCC[Si](Cl)(Cl)Cl
Reactant: CC(=O)[O-]
Agent: [Na+]
Solvent: CCCCCCC
Product: CCCCCCCC[Si](OC(C)=O)(OC(C)=O)OC(C)=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 84 %

Procedure:
In a 1-1 round-bottomed flask were placed first 55 g of anhydrous sodium acetate, and then 500 ml of anhydrous heptane. To the white suspension formed was added 50 g of octyltrichlorosilane. The reaction medium was left under stirring at ambient temperature for 2 h, and then filtered under argon to remove the precipitate. The filtrate was concentrated to eliminate the heptane, giving 54 g (88% yield) of octyltriacetoxysilane as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][CH2:7][C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14]C)=[O:13])=[CH:10][C:9]=2[C:18]([O:20][CH3:21])=[O:19])=[CH:4][CH:3]=1.O1CCOCC1.CO.[OH-].[Na+]>O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C:8]2[CH:17]=[CH:16][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=2[C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=1
Reactant: COC(=O)c1ccc(CCc2ccc(F)cc2)c(C(=O)OC)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Solvent: CO
Product: COC(=O)c1cc(C(=O)O)ccc1CCc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 86.2 %

Procedure:
A mixture of methyl 4-(4-fluorophenethyl)-3-methoxycarbonylbenzoate (51.00 g., 161.22 mmol), dioxane (650 ml), methanol (650 ml), sodium hydroxide (7.10 g., 177.35 mmol) and water (100 ml) was stirred at ambient temperature under an inert atmosphere for 16 hours. The reaction was evaporated to dryness, water (500 ml) added to the residue and the mixture extracted with diethylether. The organic extracts were dried and evaporated to dryness to give recovered methyl 4-(4-fluorophenethyl)-3-methoxycarbonylbenzoate (7 g). The aqueous layer was acidified to pH 2 with 2M HCl (300 ml) and extracted with ethyl acetate (300 ml). The organic extracts were dried, filtered and evaporated to dryness to give, as a white solid, 4-(4-fluorophenethyl)-3-methoxycarbonylbenzoic acid (42.00 g).
Reaction SMILES: C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:21]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[CH:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)(=O)=O)C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[CH:23]1([CH:22]=[C:21]([C:11]2[NH:10][C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=2)[C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:30][CH:29]=2)[CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: COc1cnc2c(c1)cc(C(=CC1CCCC1)c1ccc(C(F)(F)F)cc1)n2S(=O)(=O)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1cnc2[nH]c(C(=CC3CCCC3)c3ccc(C(F)(F)F)cc3)cc2c1
Yield: 100.9 %

Procedure:
A solution of 1-benzenesulfonyl-2-[2-cyclopentyl-1-(4-trifluoromethyl-phenyl)-vinyl]-5-methoxy-1H-pyrrolo[2,3-b]pyridine (260 mg, 0.49 mmol) in tetrahydrofuran (0.5 mL) and a tetrabutylammonium fluoride solution in tetrahydrofuran (1 M, 2 mL, 2 mmol) were stirred at room temperature for 12 h. The mixture was diluted with ethyl acetate (150 mL), and washed with a saturated aqueous ammonium chloride solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford 2-[2-cyclopentyl-1-(4-trifluoromethyl-phenyl)-vinyl]-5-methoxy-1H-pyrrolo[2,3-b]pyridine (191 mg, quant.) as a white solid: LC/MS m/e calcd for C22H21F3N2O [M+H]+ 387.42, observed 387.2.
Reaction SMILES: CCN=C=NCCCN(C)C.[C:12]([O:16][C:17]([N:19]1[CH2:22][CH:21]([NH2:23])[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].[F:24][C:25]([F:44])([F:43])[C:26]1[CH:27]=[C:28]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[C:29]([NH:31][CH2:32][C:33](O)=[O:34])=[O:30]>>[C:12]([O:16][C:17]([N:19]1[CH2:22][CH:21]([NH:23][C:33](=[O:34])[CH2:32][NH:31][C:29](=[O:30])[C:28]2[CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=[C:26]([C:25]([F:24])([F:43])[F:44])[CH:27]=2)[CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]
Reactant: O=C(O)CNC(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: CC(C)(C)OC(=O)N1CC(N)C1
Agent: CCN=C=NCCCN(C)C
Product: CC(C)(C)OC(=O)N1CC(NC(=O)CNC(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)C1

Procedure:
The title compounds were prepared as white solids from the EDCI coupling between 3-amino-azetidine-1-carboxylic acid tert-butyl ester and (3,5-bistrifluoromethyl-benzoylamino)-acetic acid (analog synthesis by following the procedure on Organic Synthesis XII, 40-2, 1932) using the procedure described in Step F of Example 1.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[NH2:19])([CH3:4])([CH3:3])[CH3:2].C([O:25][C:26](=O)[CH2:27][C:28](=[O:40])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([N:35]2[CH:39]=[CH:38][CH:37]=[N:36]2)[CH:30]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([C:15]([F:18])([F:17])[F:16])=[CH:10][C:9]=1[NH:19][C:26](=[O:25])[CH2:27][C:28](=[O:40])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([N:35]2[CH:39]=[CH:38][CH:37]=[N:36]2)[CH:30]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-n2cccn2)c1
Reactant: Cc1cc(NC(=O)OC(C)(C)C)c(N)cc1C(F)(F)F
Product: Cc1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-n3cccn3)c2)cc1C(F)(F)F

Procedure:
The title compound was prepared (2-amino-5-methyl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J15) (290 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-1-yl-phenyl)-propionic acid tert-butyl ester (Example K12) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a white solid (370 mg, 74%).
Reaction SMILES: [CH2:1]([O:8][N:9]1[C:14]([CH3:16])([CH3:15])[CH2:13][CH:12]([NH2:17])[CH2:11][C:10]1([CH3:19])[CH3:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH2:20]([CH:32]1[CH2:37][C:36](=O)[O:35][C:33]1=[O:34])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]>>[CH2:1]([O:8][N:9]1[C:14]([CH3:16])([CH3:15])[CH2:13][CH:12]([N:17]2[C:36](=[O:35])[CH2:37][CH:32]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[C:33]2=[O:34])[CH2:11][C:10]1([CH3:18])[CH3:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCCCCCCCC1CC(=O)OC1=O
Reactant: CCCCCCCON1C(C)(C)CC(N)CC1(C)C
Product: CCCCCCCCCCCCC1CC(=O)N(C2CC(C)(C)N(OCCCCCCC)C(C)(C)C2)C1=O

Procedure:
The procedure of Example 75 is repeated using 1-heptyloxy-4-amino-2,2,6,6-tetramethylpiperidine and n-dodecyl succinic anhydride to afford the title compound.
Reaction SMILES: [ClH:1].[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][NH2:9])[CH:3]=1.ClC1C=C(N2[C:22]([C:23]3[CH:28]=[C:27]([O:29][C:30]([F:33])([F:32])[F:31])[CH:26]=[C:25](F)[CH:24]=3)=[CH:21][C:20]([C:35]([OH:37])=[O:36])=N2)C=CC=1F>>[Cl:1][C:25]1[CH:24]=[C:23]([C:22]2[N:8]([C:4]3[CH:3]=[N:2][CH:7]=[CH:6][CH:5]=3)[N:9]=[C:20]([C:35]([OH:37])=[O:36])[CH:21]=2)[CH:28]=[C:27]([O:29][C:30]([F:33])([F:32])[F:31])[CH:26]=1
Reactant: O=C(O)c1cc(-c2cc(F)cc(OC(F)(F)F)c2)n(-c2ccc(F)c(Cl)c2)n1
Reactant: Cl
Reactant: NNc1cccnc1
Product: O=C(O)c1cc(-c2cc(Cl)cc(OC(F)(F)F)c2)n(-c2cccnc2)n1

Procedure:
500 mg (1.23 mmol) of the compound from example 2A is reacted with 197 mg (1.36 mmol) 3-pyridylhydrazine hydrochloride in a manner analogous to the synthesis of the compound from example 8A. Following hydrolysis, 203 mg (43% of theoretical yield) of the title compound is produced.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=O)[CH:12]=2)[CH2:7]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH3:1][O:2][C:3]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH2:15][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[CH:12]=2)[CH2:7]1
Reactant: COc1ccc(CN2Cc3ccc(C(=O)N4CCOCC4)cc3C2)c(OC)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(CN2Cc3ccc(CN4CCOCC4)cc3C2)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 33.6 %

Procedure:
A solution of [2-(2,4-dimethoxybenzyl)-2,3-dihydro-1H-isoindol-5-yl]-morpholin-4-yl-methanone (1.05 g; 2.75 mmol) in dry THF (20 ml) under a nitrogen atmosphere was treated with 1M lithium aluminium hydride solution then stirred at room temperature overnight. The reaction was quenched by the cautious addition of saturated sodium sulphate solution, then diluted with EtOAc (40 ml), filtered through Celite™ and evaporated. Purification by flash column chromatography (2% then 5% MeOH/DCM as eluant) gave 340 mg of 2-(2,4-dim ethoxybenzyl)-5-morpholin-4-ylmethyl-2,3-dihydro-1H-isoindole as a pale brown gum.
Reaction SMILES: [CH2:1](I)[CH2:2][CH3:3].[C:5]1([C:11]2[C:16](=[O:17])[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][NH:13][N:12]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>>[C:5]1([C:11]2[C:16](=[O:17])[C:15]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:14][N:13]([CH2:1][CH2:2][CH3:3])[N:12]=2)[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: O=c1c(-c2ccccc2)c[nH]nc1-c1ccccc1
Reactant: CCCI
Product: CCCn1cc(-c2ccccc2)c(=O)c(-c2ccccc2)n1
Yield: 95 %

Procedure:
Propyl iodide was reacted with 3,5-diphenyl-4(1H)-pyridazinone according to the process of Example 4 to produce 3,5-diphenyl-1-propyl-4(1H)-pyridazinone, m.p. 94°-96° C. in 95% yield.
Reaction SMILES: [C:1]([C:3]1[C:4]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)=[C:5]([C:14]([O:16]C)=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].[OH-].[Na+]>C1COCC1.CO.O>[C:1]([C:3]1[C:4]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)=[C:5]([C:14]([OH:16])=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2]
Reactant: COC(=O)c1sc(N2CCOCC2)c(C#N)c1-c1ccc(C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: Cc1ccc(-c2c(C(=O)O)sc(N3CCOCC3)c2C#N)cc1
Temperature: 50 °C
Reaction time: 3 h
Yield: 93 %

Procedure:
To a solution of 4 methyl 4-cyano-3-(4-methylphenyl)-5-morpholin-4-ylthiophene-2-carboxylate (0.060 g, 0.18 mmol) in THF/MeOH/water (2/1/1) (3 mL) was added sodium hydroxide (0.072 g, 1.8 mmol). The reaction mixture was allowed to stir at 50° C. for 3 h and was concentrated. The residue was acidified with 2N HCl and extracted with EtOAc. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The crude product was triturated with diethyl ether and hexanes to give 4-cyano-3-(4-methylphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid (4) (0.055 g, 93%). LCMS: (FA) ES+ 329.0. 1H NMR (400 MHz, d6-DMSO) δ: 7.20-7.23 (m, 4H), 3.76-3.79 (m, 4H), 3.56-3.59 (m, 4H) and 2.35 (s, 3H).
Reaction SMILES: [N:1]([CH2:4][CH:5]1[CH2:9][O:8]C(C)(C)[O:6]1)=[N+:2]=[N-:3].Cl.[S:13](Cl)([C:16]1[CH:22]=[CH:21][C:19]([CH3:20])=[CH:18][CH:17]=1)(=[O:15])=[O:14].O>CO.C(OCC)C>[CH3:20][C:19]1[CH:21]=[CH:22][C:16]([S:13]([O:8][CH2:9][CH:5]([OH:6])[CH2:4][N:1]=[N+:2]=[N-:3])(=[O:15])=[O:14])=[CH:17][CH:18]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC1(C)OCC(CN=[N+]=[N-])O1
Agent: Cl
Solvent: CO
Solvent: CCOCC
Solvent: O
Product: Cc1ccc(S(=O)(=O)OCC(O)CN=[N+]=[N-])cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 49 %

Procedure:
4-(Azidomethyl)-2,2-dimethyl-1,3-dioxolane 13 (2.2 g, 13.99 mmol) was dissolved in methanol (25 mL). To this solution was added a solution of HCl in diethyl ether (2M, 5 mL) at 0° C. The mixture was stirred at room temperature overnight, and then concentrated under reduced pressure to afford a yellow oil which was used for the next step without purification. After drying for 0.5 hr, the residue was dissolved in CH2Cl2 (30 mL) and was treated with Bu2SnO (0.071 mg, 0.3 mmol), followed by TsCl (2.86 g, 15.0 mmol) and TEA (2.2 mL, 16 mmol). After stirring for 3 hr at room temperature, water (30 mL) was added and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (2×50 mL) and the organic layer was consecutively washed with H2O (50 mL) and brine (50 mL) and dried over MgSO4. The solvent was removed under vacuum and the residue was purified on silica gel using 33% EtOAc/hexanes as the eluent to afford 1.86 g of 14 (48% yield) as a clear, colorless oil. 1H NMR (CDCl3, 400 MHz) δ: 7.77 (d, J=8.0 Hz, 2H), 7.34 (d, J=8.0 Hz, 2H), 3.96-4.09 (m, 3H), 3.31-3.40 (m, 2H), 2.43 (s, 3H). Mass Spec (lo-res): Calc'd for C10H13N3O4S: 271.06. found: 294.1 (M+Na+).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=3)=[N:17][N:18]3[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=23)=[CH:11][CH:10]=1)(=[O:8])=[O:7])=[O:4].[CH2:35]([NH:37][CH2:38][CH3:39])[CH3:36].[I-].[Na+]>C1COCC1>[NH3:5].[CH2:35]([N:37]([CH2:38][CH3:39])[CH2:2][C:3]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=3)=[N:17][N:18]3[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=23)=[CH:11][CH:10]=1)(=[O:8])=[O:7])=[O:4])[CH3:36]
Reactant: O=C(CCl)NS(=O)(=O)c1ccc(-c2c(-c3cccc(F)c3)nn3cc(C(F)(F)F)ccc23)cc1
Reactant: CCNCC
Agent: [I-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCN(CC)CC(=O)NS(=O)(=O)c1ccc(-c2c(-c3cccc(F)c3)nn3cc(C(F)(F)F)ccc23)cc1
Product: N
Temperature: 25 °C
Reaction time: 24 h
Yield: 120.3 %

Procedure:
A mixture of N-(2-chloroacetyl)-4-[2-(3-fluorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]benzenesulfonamide (0.1 g 0.2 mmol), diethylamine (0.073 g 1 mmol) and sodium iodide (0.005 g 0.03 mmol) in dry THF (5 ml) was stirred at room temperature for 24 hr. The solvent was removed and the residues partitioned between ethyl acetate (10 ml) and water (10 ml). The organic layer was dried (MgSO4), the solvent removed and the residues were purified by SPE chromatography using a cartridge containing an ion exchange sorbent that retains amino functionality. Elution with 5% acetic acid in methanol, ethyl acetate then 2M ammonia in methanol gave the title compound as a yellow solid (0.066 g 60%). MH+: 549