Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=3)[C:9]3[C:14]([C:15]=2/[C:16](=[N:18]/[OH:19])/[NH2:17])=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:27])[O:4][N:3]=1.[H-].[Na+].[CH:30](OCC)=O>C1COCC1>[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:20]3[CH:21]=[CH:22][C:23]([OH:26])=[CH:24][CH:25]=3)[C:9]3[C:14]([C:15]=2[C:16]2[N:17]=[CH:30][O:19][N:18]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:27])[O:4][N:3]=1
Reactant: Cc1noc(C)c1-c1c(/C(N)=N/O)c2ccccc2n1-c1ccc(O)cc1
Reactant: CCOC=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1noc(C)c1-c1c(-c2ncon2)c2ccccc2n1-c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
(Z)-2-(3,5-Dimethylisoxazol-4-yl)-N-hydroxy-1-(4-hydroxyphenyl)-1H-indole-3 carboximidamide (Example 11) was dissolved in THF containing 4-Å powdered molecular sieves. The mixture was stirred for 30 min under N2. NaH (60% dispersion in mineral oil, 7.0 mg, 2.1 eq.) was added and the mixture was stirred at 60° C. for 20 min. After cooling to room temperature, ethyl formate (25.6 mg, 2.5 eq) in THF was added dropwise. The resulting mixture was heated at reflux for 1 h and then cooled to room temperature. The mixture was filtered and concentrated. The residue was filtered through silica and then purified using reversed phase HPLC to give 4-(2-(3,5-dimethylisoxazol-4-yl)-3-(1,2,4-oxadiazol-3-yl)-1H-indol-1-yl)phenol as a white powder: ES/MS m/z; 395.17 (M+H), 393.19 (M−H); NMR (acetone-d6, 500 MHz): 9.21 (s, 1H), 8.40 (m, 1H), 7.37-7.31 (m, 2H), 7.26-7.22 (m, 3H), 6.98 (m, 2H), 2.17 (s, 3H) and 1.98 (s, 3H).
Reaction SMILES: [C:1]1([C:7]([N:9]2[CH2:13][CH2:12][C@H:11]([NH:14][CH:15]3[CH2:18][N:17]([C:19]([C:21]4[CH:26]=[CH:25][C:24]([C:27]5[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=5)=[CH:23][CH:22]=4)=[O:20])[CH2:16]3)[CH2:10]2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=C(Cl)C=C(C(OO)=[O:45])C=1>C(Cl)Cl.O>[OH:45][N:14]([CH:15]1[CH2:16][N:17]([C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=3)=[CH:23][CH:22]=2)=[O:20])[CH2:18]1)[C@H:11]1[CH2:12][CH2:13][N:9]([C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:8])[CH2:10]1
Reactant: O=C(c1ccc(-c2cccc(C(F)(F)F)c2)cc1)N1CC(N[C@H]2CCN(C(=O)c3ccccc3)C2)C1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Solvent: O
Product: O=C(c1ccc(-c2cccc(C(F)(F)F)c2)cc1)N1CC(N(O)[C@H]2CCN(C(=O)c3ccccc3)C2)C1
Reaction time: 0.5 h
Yield: 11.4 %

Procedure:
To a solution of Compound 16 (60 mg, 0.12 mmol) in dry CH2Cl2 (1 mL) was added mCPBA (77%, 33 mg, 0.146 mmol) at 0° C. and the resulting mixture was stirred at this temperature for 30 min. The reaction mixture was diluted with CH2Cl2 and water. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification of the residue by flash column chromatography (silica gel, 5% MeOH/EtOAc) gave compound 54 (7 mg). MS m/z (M+Na+) 510.0, MS m/z (M+Na+) 532.0.
Reaction SMILES: [OH:1][C:2]1[C:3](=[O:22])[CH:4]=[C:5]([CH2:10][NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=2)(=[O:14])=[O:13])[O:6][C:7]=1[CH2:8][OH:9].[CH2:23](OC1C(=O)C=C(CNS(C2C=CC=CC=2)(=O)=O)OC=1CO)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:23]([O:1][C:2]1[C:3](=[O:22])[CH:4]=[C:5]([CH2:10][NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=2)(=[O:14])=[O:13])[O:6][C:7]=1[CH2:8][OH:9])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: Cc1cccc(S(=O)(=O)NCc2cc(=O)c(O)c(CO)o2)c1
Reactant: O=c1cc(CNS(=O)(=O)c2ccccc2)oc(CO)c1OCc1ccccc1
Product: Cc1cccc(S(=O)(=O)NCc2cc(=O)c(OCc3ccccc3)c(CO)o2)c1
Yield: 27.12 %

Procedure:
N-(5-Benzyloxy-6-hydroxymethyl-4-oxo-4H-pyran-2-ylmethyl)-3-methyl-benzenesulfonamide (10-04) (2.6 g, 27.12%) was synthesized as a white solid from N-(5-hydroxy-6-hydroxymethyl-4-oxo-4H-pyran-2-ylmethyl)-3-methyl-benzenesulfonamide (9-04) (7.5 g, 23.07 mmol) following the procedure described for N-(5-benzyloxy-6-hydroxymethyl-4-oxo-4H-pyran-2-ylmethyl)-benzenesulfonamide (10-01).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:10])[CH2:4][C:5]1[S:6][CH:7]=[CH:8][CH:9]=1.[C:11](OC(=O)C)(=[O:13])[CH3:12].OP(O)(O)=O>>[CH3:1][O:2][C:3](=[O:10])[CH2:4][C:5]1[S:6][C:7]([C:11](=[O:13])[CH3:12])=[CH:8][CH:9]=1
Reactant: CC(=O)OC(C)=O
Reactant: COC(=O)Cc1cccs1
Agent: O=P(O)(O)O
Product: COC(=O)Cc1ccc(C(C)=O)s1

Procedure:
A mixture of 2-thienylacetic acid methyl ester, 1.41 g. (0.01 mol) and acetic anhydride, 4.2 g. (0.04 mol) was heated at 70°-80° C. and 0.2 g. of 85% H3PO4 was added dropwise with mechanically stirring. The reaction was somewhat exothermic but cooling was not necessary. The mixture was maintained between 70°-80° C. for 3 hours, and then, poured onto ice-water followed by extraction with ether. Organic layer was washed with water several times, dried over anhyd. MgSO4 and evaporated. The residue was distilled at 2mmHg and a fraction between 160° C. and 172° C. was collected. This material was gradually crystallized and could be recrystallized from the mixture of light-petroleum and benzene. m.p. 43°-44° C. Yield; 1.39 g. (76.5%)
Reaction SMILES: [C:1]([C:3]1[CH:17]=[CH:16][C:6]([CH2:7][N:8]2[C:12]([CH2:13][CH2:14][NH2:15])=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2].[C:18]1([C:24]2[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.ON1C(=O)C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.C(Cl)CCl>CN(C=O)C>[C:1]([C:3]1[CH:17]=[CH:16][C:6]([CH2:7][N:8]2[C:12]([CH2:13][CH2:14][NH:15][C:28](=[O:29])[C:27]3[CH:31]=[CH:32][C:24]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:25][CH:26]=3)=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(Cn2cncc2CCN)cc1
Reactant: O=C(O)c1ccc(-c2ccccc2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=c1c2ccccc2nnn1O
Solvent: ClCCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: N#Cc1ccc(Cn2cncc2CCNC(=O)c2ccc(-c3ccccc3)cc2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 1-(4-cyanobenzyl)-5-aminoethylimidazole (107 mg, 0.358 mmol), 4-phenylbenzoic acid (70.9 mg, 0.358 mmol), 3-hydroxy-1,2,3-benzotriazin-4(3H)-one, (72.6 mg, 0.445 mmol) and triethylamine (0.215 mL, 1.54 mmol) in DMF (4.0 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, EDC, (83.3 mg, 0.435 mmol) and the mixture stirred for 16 hours at ambient temperature. The reaction was partitioned between sat. aq. NaHCO3 solution and EtOAc. The organic layer was dried, (Na2SO4) and the solvent evaporated in vacuo. The residue was chromatographed (Silica gel, 5% MeOH in CH2Cl2) to afford the imidazole which was converted to the HCl salt by treatment with one equivalent of HCl in aqueous acetonitrile. Evaporation of the solvent in vacuo afforded the title compound as a white solid.
Reaction SMILES: [O:1]=[S:2]1(=[O:20])[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4](NCCCC(OCC)=O)=[N:3]1.Cl.[CH2:22]([O:24][C:25](=[O:28])[CH2:26][NH2:27])[CH3:23].C(N(CC)CC)C>O1CCOCC1>[O:1]=[S:2]1(=[O:20])[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4]([NH:27][CH2:26][C:25]([O:24][CH2:22][CH3:23])=[O:28])=[N:3]1
Reactant: CCOC(=O)CCCNC1=NS(=O)(=O)c2ccccc21
Reactant: CCOC(=O)CN
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CCOC(=O)CNC1=NS(=O)(=O)c2ccccc21

Procedure:
15.0 g. (74.4 mM) of 3-chloro-1,2-benzisothiazole 1,1-dioxide (prepared as in Example 1), 10.4 g. (74.4 mM) of glycine ethyl ester, hydrochloride and 20.4 ml. (148.8 mM) of triethylamine are refluxed in 250 ml of dioxane for 2 hours. The dioxane is evaporated and the residue is taken up in chloroform which is washed with water (2 x) and evaporated. The residue 2-[(1,1-dioxo-1,2-benzisothiazol-3-yl)amino]acetic acid, ethyl ester is recrystallized once from 150 ml of methanol/water (1:1) and once from 200 ml. of water to give 2-[(1,1-dioxo-1,2-benzisothiazol-3-yl)amino]acetic acid, ethyl ester as yellow needles, yield 14.35 g., m.p. 166°-167°.
Reaction SMILES: [ClH:1].[NH2:2][CH:3]([CH:9]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[CH2:13][CH2:12][C:11]2[CH:20]=[CH:21][CH:22]=[CH:23][C:10]1=2)[C:4]([O:6]CC)=[O:5].[OH-].[K+].C(O)C>O>[ClH:1].[NH2:2][CH:3]([CH:9]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[CH2:13][CH2:12][C:11]2[CH:20]=[CH:21][CH:22]=[CH:23][C:10]1=2)[C:4]([OH:6])=[O:5]
Reactant: CCOC(=O)C(N)C1c2ccccc2CCc2ccccc21
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: NC(C(=O)O)C1c2ccccc2CCc2ccccc21
Yield: 74.4 %

Procedure:
Ethyl α-amino-10,11-dihydro-5H-dibenzo[a,d]-cycloheptene-5-acetate hydrochloride (13 g, 39 mmol) is stirred with 400 mL of IM ethanolic potassium hydroxide solution at room temperature overnight. Ethanol is stripped and the solid taken up in water, extracted with diethyl ether, and acidified with 1N hydrochloric acid to pH 1. A precipitate is collected by filtration, washed with diethyl ether, dried at 50° C./2 mm Hg to furnish 8.81 g of the title compound; mp >285° C.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][CH2:5][O:6][C:7]1[CH:23]=[CH:22][C:10]([NH:11][S:12]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[C:9]([N+:24]([O-:26])=[O:25])[CH:8]=1.S(OC)(O[CH3:31])(=O)=O.O>CN(C=O)C>[CH3:3][O:4][CH2:5][O:6][C:7]1[CH:23]=[CH:22][C:10]([N:11]([CH3:31])[S:12]([C:15]2[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=2)(=[O:14])=[O:13])=[C:9]([N+:24]([O-:26])=[O:25])[CH:8]=1
Reactant: COCOc1ccc(NS(=O)(=O)c2ccc(C)cc2)c([N+](=O)[O-])c1
Reactant: COS(=O)(=O)OC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COCOc1ccc(N(C)S(=O)(=O)c2ccc(C)cc2)c([N+](=O)[O-])c1
Temperature: 25 °C
Yield: 93.3 %

Procedure:
To a suspension of sodium hydride (60%, 0.40 g (10.0 mmol)) in 15.0 ml of DMF, 4′-methoxymethoxy-2′-nitro-p-toluenesulfonanilide (3.00 g (8.51 mmol)) was added with stirring at room temperature. To the resulting mixture, after 15 minutes' stirring at room temperature, dimethyl sulfate (1.0 ml (10.6 mmol)) was added and the mixture was stirred for 15 hours at room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was then subjected to silica gel column chromatography with ethyl acetate-hexane (1:2) to give 2.91 g (93%) of the title compound as yellow crystals.
Reaction SMILES: [C:1]1(C)C=CC=C[CH:2]=1.[N+:8]([C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[CH:13][CH:12]=1)([O-:10])=[O:9]>O.FC(F)C(F)(F)S(O)(=O)=O.C(O)C>[N+:8]([C:11]1[CH:12]=[CH:13][C:14]([C:15]([O:17][CH2:1][CH3:2])=[O:16])=[CH:18][CH:19]=1)([O-:10])=[O:9]
Reactant: Cc1ccccc1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: O=S(=O)(O)C(F)(F)C(F)F
Solvent: O
Solvent: CCO
Product: CCOC(=O)c1ccc([N+](=O)[O-])cc1
Yield: 90 %

Procedure:
700 g of toluene, 190 g of ethanol, 350 g of 4-nitrobenzoic acid and 7 g of tetrafluoroethanesulfonic acid hydrate are weighed into a 2-1 four-necked flask equipped as described in Example 1. The procedure described in Example 1 is then repeated. Using the work-up described in Example 1 gives 368 g of ethyl 4-nitrobenzoate and, after drying, 361 g of dry ethyl 4-nitrobenzoate, which corresponds to a yield of 88.3% of theory, in a purity of 98.9% by HPLC.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)/[CH:9]=[CH:10]/[C:11]2[S:15][CH:14]=[N:13][C:12]=2[CH3:16])=[CH:4][C:3]=1[CH3:18].[NH2:19][C:20]([NH2:22])=[O:21]>Cl.O1CCOCC1>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:11]3[S:15][CH:14]=[N:13][C:12]=3[CH3:16])[NH:22][C:20](=[O:21])[N:19]=2)=[CH:4][C:3]=1[CH3:18]
Reactant: NC(N)=O
Reactant: Cc1cc(C(=O)/C=C/c2scnc2C)ccc1O
Agent: Cl
Solvent: C1COCCO1
Product: Cc1cc(-c2cc(-c3scnc3C)[nH]c(=O)n2)ccc1O
Temperature: 120 °C
Yield: 3.3 %

Procedure:
(((E)-1-(4-hydroxy-3-methylphenyl)-3-(4-methylthiazol-5-yl)prop-2-en-1-one (200 mg, 0.77 mmol) and urea (0.23 g, 3.8 mmol) were suspended in 5 mL of 4N HCl solution in dioxane (Aldrich), and the reaction mixture was heated in a sealed vessel to 120° C. for 20 h. After cooling to room temperature, the resulting mixture was concentrated in vacuo to remove dioxane. The residue was dissolved in 5 mL of methanol, and the product was purified by preparative HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid) to yield 7.7 mg of 4-(4-hydroxy-3-methylphenyl)-6-(4-methyl-1,3-thiazol-5-yl)pyrimidin-2(1H)-one. 1H NMR (400 MHz, d6-DMSO): δ 9.11 (s, 1H), 7.81 (d, 1H), 7.72 (dd, 1H), 7.07 (s, 1H), 6.90 (d, 1H), 2.73 (s, 3H), 2.17 (s, 3H). MS (EI) for C15H13N3O2S: 300.4 (MH+).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[C:12]([C:18]([OH:20])=O)[NH:13]3)[CH:5]=[CH:4][CH:3]=1.Cl.Cl.Cl.[N:24]1([CH2:31][CH2:32][N:33]2[CH2:38][CH2:37][CH:36]([NH2:39])[CH2:35][CH2:34]2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>>[N:24]1([CH2:31][CH2:32][N:33]2[CH2:34][CH2:35][CH:36]([NH:39][C:18]([C:12]3[NH:13][C:14]4[C:10]([CH:11]=3)=[C:9]([O:8][C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([Cl:1])[N:7]=3)[CH:17]=[CH:16][CH:15]=4)=[O:20])[CH2:37][CH2:38]2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: O=C(O)c1cc2c(Oc3cccc(Cl)n3)cccc2[nH]1
Reactant: NC1CCN(CCN2CCCCCC2)CC1
Agent: Cl
Product: O=C(NC1CCN(CCN2CCCCCC2)CC1)c1cc2c(Oc3cccc(Cl)n3)cccc2[nH]1

Procedure:
This compound is synthesized analogously to Example 1 from 4-(6-Chloro-pyridin-2-yloxy)-1H-indole-2-carboxylic acid 157 (preparation see below) and amine 5.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([CH:13]=[O:14])[N:10]=[C:9]1[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][Mg]Cl.[Cl-].[NH4+]>O1CCCC1>[CH2:1]([N:8]1[CH:12]=[C:11]([CH:13]([OH:14])[CH3:16])[N:10]=[C:9]1[CH3:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[Mg]Cl
Reactant: Cc1nc(C=O)cn1Cc1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: Cc1nc(C(C)O)cn1Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 7.2 g (0.306 mole) of 1-benzyl-2-methylimidazol-4-carboxaldehyde in 100 ml of tetrahydrofuran was added 15 ml of 2.9M methyl magnesium chloride (0.044 mole) in tetrahydrofuran. A white precipitate formed immediately. The mixture was stirred at room temperature for 30 minutes and then heated with 50 ml of 25% aqueous ammonium chloride solution. The precipitate was filtered off, washed with tetrahydrofuran and air dried. The combined filtrate and wash solutions were dried (Na2SO4) and concentrated in vacuo to a solid residue. The residue was dissolved in 300 ml of boiling ethyl acetate, dried (Na2SO4) and concentrated to half volume under reduced pressure. The solid which separated upon cooling was filtered off and air dried. Total yield=7.1 g (90%); m.p. 162.5°-167.5° C.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11](O)=[O:12])=[CH:10][C:5]=2[N:4]=[C:3]1[NH:14][C:15]1[S:16][C:17]2[CH:23]=[C:22]([O:24][C:25]([F:28])([F:27])[F:26])[CH:21]=[CH:20][C:18]=2[N:19]=1.[NH2:29][CH2:30][CH:31]([OH:33])[CH3:32].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>>[OH:33][CH:31]([CH3:32])[CH2:30][NH:29][C:11]([C:9]1[CH:8]=[CH:7][C:6]2[N:2]([CH3:1])[C:3]([NH:14][C:15]3[S:16][C:17]4[CH:23]=[C:22]([O:24][C:25]([F:27])([F:26])[F:28])[CH:21]=[CH:20][C:18]=4[N:19]=3)=[N:4][C:5]=2[CH:10]=1)=[O:12]
Reactant: CC(O)CN
Reactant: Cn1c(Nc2nc3ccc(OC(F)(F)F)cc3s2)nc2cc(C(=O)O)ccc21
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: CC(O)CNC(=O)c1ccc2c(c1)nc(Nc1nc3ccc(OC(F)(F)F)cc3s1)n2C
Yield: 58.8 %

Procedure:
1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-hydroxy-propyl)-amide (67 mg) was prepared by following General Procedure F starting from 1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (100 mg), 1-amino-2-propanol (20 mg), HBTU (111 mg), and DIEA (64 uL). LC/MS: m/z 466.9. 1H NMR (DMSO-d6, 400 MHz): δ 12.40 (bs, 1H), 8.35 (s, 1H), 8.09 (s, 1H), 7.92 (s, 1H), 7.86-7.66 (m, 2H), 7.48 (d, 1H), 7.36 (d, 1H), 4.77 (d, 1H), 3.87-3.77 (m, 1H), 3.64 (bs, 3H), 3.29-3.17 (m, 2H), 1.09 (d, 3H).
Reaction SMILES: [CH:1]([O:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][OH:24])=[CH2:2].[OH-].[Na+].[CH3:27]I>>[CH:1]([O:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH3:27])=[CH2:2]
Reactant: C=COCCOCCOCCOCCOCCOCCOCCO
Reactant: CI
Agent: [Na+]
Agent: [OH-]
Product: C=COCCOCCOCCOCCOCCOCCOCCOC
Temperature: 40 °C
Reaction time: 5 h

Procedure:
A 1-L flask equipped with a stirrer, a dropping funnel, a thermometer, a condenser tube, and a nitrogen gas inlet was charged with 50 parts of heptaethylene glycol vinyl ether and 11 parts of sodium hydroxide. The flask was heated to 40° C. with stirring under a nitrogen atmosphere, and then 40 parts of methyl iodide was slowly dropped while the internal temperature was maintained at 40° C. or lower. After completion of the dropping, the mixture was aged for five hours, and distilled under reduced pressure so that unreacted methyl iodide was removed. In order to further remove sodium hydroxide in excess and water and sodium iodide generated after the reaction, adsorption treatment was performed using an adsorbent, and thereby heptaethylene glycol methyl vinyl ether was obtained.
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[CH:15]([C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=1)=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[CH3:24][O:23][C:21]([C:20]1[CH:25]=[CH:26][C:17]([CH2:15][NH:1][CH2:2][CH:3]2[CH2:7][CH2:6][CH2:5][N:4]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[CH:18][CH:19]=1)=[O:22]
Reactant: CC(C)(C)OC(=O)N1CCCC1CN
Reactant: COC(=O)c1ccc(C=O)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(Cl)Cl
Solvent: CC(=O)O
Product: COC(=O)c1ccc(CNCC2CCCN2C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 45.9 %

Procedure:
A solution of 1,1-dimethylethyl 2-(aminomethyl)-1-pyrrolidinecarboxylate (1000 mg, 5 mmol) and methyl 4-formylbenzoate (820 mg, 5 mmol) in dichloroethane was stirred as acetic acid (450 mg, 7.5 mmol) and sodium triacetoxyborohydride (1271 mg, 6 mmol) were added sequentially at ambient temperature. After stirring at ambient temperature for 17 hours, treated with a saturated aqueous solution of sodium bicarbonate and extracted with EtOAc. The combined organic extracts were dried and concentrated. Purification by flash chromatography afforded 1,1-dimethylethyl 2-[[[[4-(methoxycarbonyl)phenyl]methyl]amino]methyl]-1-pyrrolidinecarboxylate (800 mg), 1H NMR (CDCl3) 7.98 (d, 2H), 3.37 (d, 2H), 3.91 (s, 3H), 3.82 (s, 2H), 3.36 (m, 2H), 2.72 (m, 1H), 1.82 (m, 3H), 1.44 (m, 2H) ppm.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][CH:3]=1.O.[SH-:13].[Na+]>CN(C=O)C>[CH3:11][S:8]([C:5]1[CH:6]=[CH:7][C:2]([SH:13])=[CH:3][CH:4]=1)(=[O:10])=[O:9]
Reactant: CS(=O)(=O)c1ccc(F)cc1
Reactant: [SH-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CS(=O)(=O)c1ccc(S)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 105.7 %

Procedure:
1-Fluoro-4-(methylsulfonyl)-benzene (1.74 g) and sodium hydrosulphide hydrate (0.67 g) were dissolved in DMF (10 ml) and stirred at room temperature for 24 hours. The reaction was quenched with water, acidified with 2M hydrochloric acid (20 ml) and extracted with ethyl acetate (2×50 ml). The combined extracts were then washed with water (2×25 ml) and brine (20 ml). The organic solution was dried (MgSO4), filtered and evaporated in vacuo to yield the sub-title compound as a white solid (1.8 g).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[C:8]3[CH2:9][NH:10][C:11](=[O:23])[C:12]=3[CH:13]=[C:14]3[CH:22]=[CH:21][C:20]4[O:19][CH2:18][O:17][C:16]=4[C:15]=23)=[CH:3][CH:2]=1.[CH3:24][I:25]>CO>[I-:25].[O:17]1[C:16]2[C:15]3[C:14]([CH:22]=[CH:21][C:20]=2[O:19][CH2:18]1)=[CH:13][C:12]1[C:11](=[O:23])[NH:10][CH2:9][C:8]=1[C:7]=3[C:4]1[CH:5]=[CH:6][N+:1]([CH3:24])=[CH:2][CH:3]=1
Reactant: CI
Reactant: O=C1NCc2c1cc1ccc3c(c1c2-c1ccncc1)OCO3
Solvent: CO
Product: C[n+]1ccc(-c2c3c(cc4ccc5c(c24)OCO5)C(=O)NC3)cc1
Product: [I-]

Procedure:
To a methanol (10 ml) solution of 8,9-dihydro-10-(4-pyridyl)-7H-1,3-benzodioxolo[4,5-f]isoindol-7-one (63 mg) was added methyl iodide (3 ml) and heated under reflux for 3 hours. The resultant precipitates were collected by suction and recrystallized from methanol-THF to give the entitled compound (51 mg) as yellow crystals.
Reaction SMILES: C([N:3](CC)[CH:4]=[C:5]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:6](=[O:15])[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=O)C.[NH2:24]N>C(O)(C)C>[C:9]1([C:7]2[C:6](=[O:15])[C:5]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:4][NH:3][N:24]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: NN
Reactant: CCN(C=C(C(=O)C(=O)c1ccccc1)c1ccccc1)CC
Solvent: CC(C)O
Product: O=c1c(-c2ccccc2)c[nH]nc1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
The product solution from Example 1 was cooled to 0°C. and mixed with 20 ml. of isopropyl alcohol and 2 ml. of hydrazine. The mixture was stirred for 10 minutes, and was then warmed to room temperature and stirred for 15 hours. The product was then collected by filtration. The yield was 6.0 g. of 3,5-diphenyl-4(1H)-pyridazinone, m.p. 328°-32°C., which was identified by infrared and nuclear magnetic resonance analysis.
Reaction SMILES: [NH4+:1].[NH4+].[O-:3][Mo:4]([O-])(=O)=O.[Mo:8](=O)(=O)=[O:9]>O>[NH3:1].[NH3:1].[NH3:1].[NH3:1].[NH3:1].[NH3:1].[OH2:3].[OH2:9].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[OH2:3].[Mo:4].[Mo:8].[Mo:4].[Mo:4].[Mo:4].[Mo:4].[Mo:4]
Reactant: O=[Mo](=O)([O-])[O-]
Reactant: [NH4+]
Reactant: O=[Mo](=O)=O
Solvent: O
Product: N
Product: [Mo]
Temperature: 25 °C
Reaction time: 2 h

Procedure:
4H2O (AHM) was dissolved in 15 g of fresh deionized water. 25 g of the activated carbon was impregnated with this solution to incipient wetness. It was left at room temperature with occasional stirring for 2 hours. It was then heated slowly at 0.3° C./min to 115° C. in a temperature programmable forced air circulation oven, was left at that temperature for 24 hours, and then cooled slowly to room temperature in about 3 hours time. The resulting material is referred to as catalyst C1. The Mo in catalyst C1 exists probably as partially decomposed ammonium molybdate. If all the AHM would have decomposed to Mo trioxide, it would contain 16.2% by weight molybdenum trioxide, the balance being carbon support.
Reaction SMILES: [C:1]([O:15]CC)(=O)[CH2:2][O:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH3:13].O.[NH2:19][NH2:20]>C(O)C>[C:1]([NH:19][NH2:20])(=[O:15])[CH2:2][O:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH3:13]
Reactant: CCOC(=O)COCCOCCOCCOC
Reactant: NN
Solvent: CCO
Solvent: O
Product: COCCOCCOCCOCC(=O)NN
Reaction time: 25 h

Procedure:
A solution of 61 g (0.244 mol) of crude ethyl 3,6,9,12-tetra-oxa-tridecanoate and 25 ml (0.488 mol) of hydrazine hydrate in 600 ml of ethanol is left to stand for 25 hours at 25°. The reaction mixture is evaporated and the crude, oily 3,6,9,12-tetra-oxa-tridecanoic acid hydrazide, which is thus obtained, is further processed direct.