Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1](Br)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:10][CH:11]1[C:15]23[CH:23]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:22]=[CH:21][CH:20]=[C:16]2[N:17]=[CH:18][CH:19]=[C:14]3[S:13][CH2:12]1.Cl>C(O)(C)C.CO>[CH3:10][CH:11]1[C:15]23[CH:23]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH:22]=[CH:21][CH:20]=[C:16]2[N:17]=[CH:18][CH:19]=[C:14]3[S:13][CH:12]1[CH2:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CC1CSC2=CC=NC3=CC=CC(c4ccccc4)C321
Reactant: BrCCc1ccccc1
Agent: Cl
Solvent: CC(C)O
Solvent: CO
Product: CC1C(CCc2ccccc2)SC2=CC=NC3=CC=CC(c4ccccc4)C321

Procedure:
Phenethyl bromide is condensed with 3-methyl-4-phenyl-1,2,3,4-tetrahydro-benzo(b)thieno[3,2-c]pyridine (Example 2) according to the procedure described in Example 6. Hydrochloride: white crytals, m.p. 210° C. (isopropanol-methanol); Yield : 72%.
Reaction SMILES: [CH3:1][N:2]1[C:6]([NH2:7])=[CH:5][C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[N:3]1.[Br:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=O)=[C:17]([CH3:23])[CH:16]=1.O.CC1C=CC(S(O)(=O)=O)=CC=1>CC#N>[Br:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[C:5]2[C:6](=[NH:7])[N:2]([CH3:1])[N:3]=[C:4]2[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)=[C:17]([CH3:23])[CH:16]=1
Reactant: Cc1cc(Br)ccc1C=O
Reactant: Cn1nc(-c2ccccn2)cc1N
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CC#N
Product: Cc1cc(Br)ccc1C=C1C(=N)N(C)N=C1c1ccccn1
Temperature: 45 °C
Yield: 64.1 %

Procedure:
A suspension of 1-methyl-3-(pyridin-2-yl)-1H-pyrazol-5-amine (4.50 g, 25.8 mmol, Example #2 step B), 4-bromo-2-methylbenzaldehyde (5.14 g, 25.8 mmol, Astatech) and 4-methylbenzenesulfonic acid hydrate (0.491 g, 2.58 mmol) in MeCN (36 ml) was warmed up to about 45° C. for about 15 min to give a solution then the reaction was allowed to cool to rt. The precipitate was filtered and washed with MeCN to give 4-(4-bromo-2-methylbenzylidene)-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-5(4H)-imine (5.88 g, 16.55 mmol, 64%) as a beige solid: LC-MS (Table 1, Method g) Rt=2.55 min, m/z 355/357 (M+H)+; 1H-NMR (DMSO-d6, Bruker 400 MHz) δ 9.07 (s, 1H), 8.60-8.57 (m, 1H), 8.02-7.95 (m, 2H), 7.91-7.86 (m, 1H), 7.61-7.50 (m, 2H), 7.40-7.31 (m, 1H), 7.19 (s, 1H), 3.96 (s, 3H), 2.62 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1([C:7]2[S:11][C:10]([CH2:12][N:13]3[N:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([C:27]2[O:31][CH:30]=[N:29][C:28]=2[C:32](O)=[O:33])[CH:24]=[CH:25][CH:26]=1>>[C:2]([C:7]1[S:11][C:10]([CH2:12][N:13]2[N:17]=[C:16]([NH:18][C:32]([C:28]3[N:29]=[CH:30][O:31][C:27]=3[C:23]3[CH:24]=[CH:25][CH:26]=[C:21]([O:20][CH3:19])[CH:22]=3)=[O:33])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: COc1cccc(-c2ocnc2C(=O)O)c1
Reactant: CC1(c2ccc(Cn3ncc(N)n3)s2)OCCO1
Product: COc1cccc(-c2ocnc2C(=O)Nc2cnn(Cc3ccc(C(C)=O)s3)n2)c1

Procedure:
Following general procedure A followed by B, starting from 2-[5-(2-methyl-[1,3]dioxolan-2-yl)-thiophen-2-ylmethyl]-2H-[1,2,3]triazol-4-ylamine and 5-(3-methoxy-phenyl)-oxazole-4-carboxylic acid.
Reaction SMILES: [O:1]=[S:2]1(=[O:15])[CH:6]([CH2:7][CH2:8][CH3:9])[C:5]2[C:10]([Cl:14])=[CH:11][CH:12]=[CH:13][C:4]=2[NH:3]1.[N+:16]([O-])([O-:18])=[O:17].[NH4+].FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)(Cl)Cl>[O:15]=[S:2]1(=[O:1])[CH:6]([CH2:7][CH2:8][CH3:9])[C:5]2[C:10]([Cl:14])=[CH:11][CH:12]=[C:13]([N+:16]([O-:18])=[O:17])[C:4]=2[NH:3]1
Reactant: O=[N+]([O-])[O-]
Reactant: CCCC1c2c(Cl)cccc2NS1(=O)=O
Agent: [NH4+]
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: ClC(Cl)Cl
Product: CCCC1c2c(Cl)ccc([N+](=O)[O-])c2NS1(=O)=O
Reaction time: 24 h
Yield: 17.8 %

Procedure:
1,3-dihydro-2,2-dioxo-4-chloro-3-propyl-2,1 -benzisothiazole (131 mg, 0.54 mmol) was dissolved in chloroform (30 ml) followed by the addition of ammonium nitrate (44 mg, 0.54 mmol) and trifluoroacetic anhydride (397 mg, 214.4 mmol). The mixture is allowed to stir. After 24 hours, the reaction mixture is diluted with chloroform and extracted with water. The organic layer is dried over MgSO4 and filtered. The solvent was evaporated and chromatography of the resulting solid on silica gel (50% Ethyl acetate/Hexane) gave the desired product (28 mg, 20%). EI-MS m/z 289.1 (M+).
Reaction SMILES: C([O:5][C:6]1[CH:37]=[CH:36][C:9]([CH2:10][CH:11]2[NH:20][C:19](=[O:21])[NH:18][CH:17]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29]C(C)(C)C)=[CH:25][CH:24]=3)[CH:16]3[CH:12]2[O:13]C(C)(C)[O:15]3)=[CH:8][CH:7]=1)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[OH:13][CH:12]1[CH:16]([OH:15])[CH:17]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([OH:29])=[CH:27][CH:28]=2)[NH:18][C:19](=[O:21])[NH:20][CH:11]1[CH2:10][C:9]1[CH:8]=[CH:7][C:6]([OH:5])=[CH:37][CH:36]=1
Reactant: CC(C)(C)Oc1ccc(CC2NC(=O)NC(Cc3ccc(OC(C)(C)C)cc3)C3OC(C)(C)OC23)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C1NC(Cc2ccc(O)cc2)C(O)C(O)C(Cc2ccc(O)cc2)N1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Cyclic Urea 2.8 (0.4 g, 0.78 mmol) was dissolved in dichloromethane (3 mL) and treated with TFA (1 mL). The mixture was stirred at room temperature for 2 h upon which time a white solid precipitated. 2 drops of water and methanol (2 mL) were added and the homogeneous solution was stirred for 1 h and concentrated under reduced pressure. The crude solid, 2.9, was dried overnight and then used without further purification.
Reaction SMILES: [CH2:1]([C:3]1[C:11]2[N:10]3[CH:12]=[CH:13][CH:14]=[C:9]3[CH:8]=[N:7][C:6]=2[N:5](COCC[Si](C)(C)C)[C:4]=1[C:23]1[CH:28]=[CH:27][C:26]([C:29]2([CH3:34])OCC[O:30]2)=[CH:25][CH:24]=1)[CH3:2].Cl.C(O)(C(F)(F)F)=O.[NH4+].[OH-]>CC(C)=O.C(Cl)Cl>[CH2:1]([C:3]1[C:11]2[N:10]3[CH:12]=[CH:13][CH:14]=[C:9]3[CH:8]=[N:7][C:6]=2[NH:5][C:4]=1[C:23]1[CH:28]=[CH:27][C:26]([C:29](=[O:30])[CH3:34])=[CH:25][CH:24]=1)[CH3:2]
Reactant: CCc1c(-c2ccc(C3(C)OCCO3)cc2)n(COCC[Si](C)(C)C)c2ncc3cccn3c12
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: CC(C)=O
Product: CCc1c(-c2ccc(C(C)=O)cc2)[nH]c2ncc3cccn3c12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 60.1 %

Procedure:
1-Ethyl-2-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-dipyrrolo[1,2-a:2′,3′-e]pyrazine (0.194 g, 0.406 mmol) was dissolved in acetone (6 mL) then treated with concentrated aqueous HCl (36 wt %, 0.170 mL, 2.08 mmol). The mixture was stirred at rt for 30 min. The solvents were evaporated under reduced pressure and then the material was treated with DCM (3 mL) and TFA (1.5 mL, 19 mmol). The mixture was stirred at rt for about 15 min then the solvents were evaporated under reduced pressure. The residue was dissolved in 1,4-dioxane (4 mL) then treated with concentrated aqueous NH4OH (26 wt %, 2 mL, 13.87 mmol). The mixture was stirred at rt for 30 min then warmed to about 50° C. for about 15 min. The mixture was cooled to rt and the solvents removed under reduced pressure. The material was treated with water (15 mL) then stirred for about 5 min at rt. The solids were collected by filtration then dried under vacuum at about 60° C. to a constant weight to give 1-(4-(1-ethyl-3H-dipyrrolo[1,2-a:2′,3′-e]pyrazin-2-yl)phenyl)ethanone (0.074 g, 60%): LC/MS (Table 2, Method b) Rt=2.37 min; MS m/z 304 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C@@H:14]([NH:21][C:22](=[O:42])[CH2:23][NH:24][C:25](=[O:41])[C:26]2[CH:31]=[C:30]([NH:32][C:33]3[NH:34][CH2:35][CH:36]([OH:39])[CH2:37][N:38]=3)[CH:29]=[C:28]([OH:40])[CH:27]=2)[CH2:15][C:16]([O:18]CC)=[O:17])[CH:5]=[C:6]([C:8]2([CH:11]([F:13])[F:12])[CH2:10][CH2:9]2)[CH:7]=1.O.[OH-].[Li+].ClCCl>C(#N)C.O.O>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:14]([NH:21][C:22](=[O:42])[CH2:23][NH:24][C:25](=[O:41])[C:26]2[CH:31]=[C:30]([NH:32][C:33]3[NH:38][CH2:37][CH:36]([OH:39])[CH2:35][N:34]=3)[CH:29]=[C:28]([OH:40])[CH:27]=2)[CH2:15][C:16]([OH:18])=[O:17])[CH:5]=[C:6]([C:8]2([CH:11]([F:13])[F:12])[CH2:10][CH2:9]2)[CH:7]=1
Reactant: CCOC(=O)C[C@H](NC(=O)CNC(=O)c1cc(O)cc(NC2=NCC(O)CN2)c1)c1cc(Br)cc(C2(C(F)F)CC2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Solvent: CC#N
Product: O=C(O)C[C@H](NC(=O)CNC(=O)c1cc(O)cc(NC2=NCC(O)CN2)c1)c1cc(Br)cc(C2(C(F)F)CC2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of (3S)-ethyl 3-(3-bromo-5-(1-(difluoromethyl)cyclopropyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoate (from step 2 above) (0.635 mmol, crude residue) in a mixture of acetonitrile/water (1:1) (6 mL) was added lithium hydroxide monohydrate (135 mg, 3.217 mmol) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated in vacuo to afford a pale yellow crystalline residue. The residue was dissolved in water (25 mL) and stirred with dichloromethane (50 mL) to remove the urea. The aqueous layer was neutralized with TFA (1 mL in 3 mL ACN) and evaporated in vacuo to afford a pale yellow viscous residue. The crude residue was purified by reverse-phase preparative HPLC on a Biotage 40+M (100 g) C18HS column and a gradient 10-60% acetonitrile in water containing 0.05% TFA to give the desired product, after lyophilization, as a colorless lyophilized powder (94.0 mg). LC-MS analysis of the product shows the desired product's mass: m/z 624 (79BrM+H) and m/z 626 (81BrM+H); Calcd for C26H28BrF2N5O6: 624.43.
Reaction SMILES: C([Si](C)(C)[O:6][C:7]1[CH:14]=[C:13]([CH3:15])[C:10]([CH:11]=[O:12])=[C:9]([CH3:16])[CH:8]=1)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[OH:6][C:7]1[CH:8]=[C:9]([CH3:16])[C:10]([CH:11]=[O:12])=[C:13]([CH3:15])[CH:14]=1
Reactant: Cc1cc(O[Si](C)(C)C(C)(C)C)cc(C)c1C=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Cc1cc(O)cc(C)c1C=O

Procedure:
To a stirred solution of 4-(tert-butyldimethyl-silanyloxy)-2,6-dimethylbenzaldehyde (2.4 g, 9 mmol) in THF (10 mL) was added TBAF (10 mL of a 1.0 M solution in THF). After an hour at ambient temperature, the reaction mixture was quenched with water and the aqueous layer was extracted with EtOAc. The organic layer was washed with water, brine, dried with MgSO4 and filtered. The solvent was removed under reduced pressure to give 4-hydroxy-2,6-dimethylbenzaldehyde as a yellow oil.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:9](=[N:25][O:26][CH:27]([CH3:29])[CH3:28])[C@@H:10]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([F:23])([F:22])[F:21])[CH3:11])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1>C(#N)C>[Cl:1][C:2]1[C:3](/[C:9](=[N:25]\[O:26][CH:27]([CH3:29])[CH3:28])/[C@@H:10]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([F:22])([F:21])[F:23])[CH3:11])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CC(C)ON=C(c1ncc(Cl)cc1Cl)[C@H](C)NC(=O)c1ccccc1C(F)(F)F
Solvent: CC#N
Product: CC(C)O/N=C(\c1ncc(Cl)cc1Cl)[C@H](C)NC(=O)c1ccccc1C(F)(F)F
Yield: 63.8 %

Procedure:
240 mg of (S)—N-[2-(3,5-dichloropyridin-2-yl)-2-(isopropoxyimino)-1-methylethyl]-2-(trifluoromethyl)benzamide was dissolved in 4 ml of acetonitrile, and the solution was irradiated with light for 8 hours in a quartz cell (manufactured by Fine, 4 clear windows for spectroscopy) using a 100 W high-pressure mercury lamp (manufactured by USHIO INC., lamp: UM-102, power supply: UM-103B-B). After completion of the reaction, the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 1:9 to 5:5) as the eluent to obtain 153 mg of the desired product as a colorless resinous substance.
Reaction SMILES: [OH-].[K+].[CH2:3]([O:5][C:6](=[O:35])[CH:7]([CH2:13][C:14]1[CH:15]=[N:16][C:17]([N:20]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[N:18][CH:19]=1)[C:8]([O:10]CC)=[O:9])[CH3:4].CCOC(C)=O>CCO.CCO.C(Cl)Cl>[CH2:3]([O:5][C:6](=[O:35])[CH:7]([CH2:13][C:14]1[CH:15]=[N:16][C:17]([N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:28]([O:30][C:31]([CH3:33])([CH3:34])[CH3:32])=[O:29])=[N:18][CH:19]=1)[C:8]([OH:10])=[O:9])[CH3:4]
Reactant: CCOC(=O)C(Cc1cnc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nc1)C(=O)OCC
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCOC(=O)C(Cc1cnc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nc1)C(=O)O
Temperature: 25 °C
Reaction time: 16 h
Yield: 89.2 %

Procedure:
A solution of KOH (106 mg, 1.88 mmol) in EtOH (2 mL) was added to a solution of 2-(2-[N,N-bis(tert-butoxycarbonyl)amino]-pyrimidin-5-ylmethyl)-malonic acid diethyl ester (0.80 g, 1.71 mmol) in EtOH/methylene chloride (2:1, 12 mL) at 0° C. The mixture was stirred for 16 h at room temperature and EtOAc was added. The mixture was washed with 0.5 M HCl and brine, dried and concentrated under reduced pressure to give 2-(2-[N,N-bis(tert-butoxycarbonyl)amino]-pyrimidin-5-ylmethyl)-malonic acid monoethyl ester (0.67 g, 89%).
Reaction SMILES: NC1(C2C=CC(C3C(=O)C4C(=CC=C(F)C=4)OC=3C3C=CC=CC=3)=CC=2)CCC1.C(OC(=O)[NH:36][C:37]1([C:41]2[CH:46]=[CH:45][C:44]([C:47]3[C:56](=[O:57])[C:55]4[C:50](=[CH:51][CH:52]=[C:53]([N:58]5[CH2:63][CH2:62][N:61]([CH3:64])[CH2:60][CH2:59]5)[CH:54]=4)[O:49][C:48]=3[C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)=[CH:43][CH:42]=2)[CH2:40][CH2:39][CH2:38]1)(C)(C)C>>[NH2:36][C:37]1([C:41]2[CH:42]=[CH:43][C:44]([C:47]3[C:56](=[O:57])[C:55]4[C:50](=[CH:51][CH:52]=[C:53]([N:58]5[CH2:63][CH2:62][N:61]([CH3:64])[CH2:60][CH2:59]5)[CH:54]=4)[O:49][C:48]=3[C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)=[CH:45][CH:46]=2)[CH2:38][CH2:39][CH2:40]1
Reactant: CN1CCN(c2ccc3oc(-c4ccccc4)c(-c4ccc(C5(NC(=O)OC(C)(C)C)CCC5)cc4)c(=O)c3c2)CC1
Agent: NC1(c2ccc(-c3c(-c4ccccc4)oc4ccc(F)cc4c3=O)cc2)CCC1
Product: CN1CCN(c2ccc3oc(-c4ccccc4)c(-c4ccc(C5(N)CCC5)cc4)c(=O)c3c2)CC1
Yield: 96 %

Procedure:
Following the procedure used to prepare 3-[4-(1-amino-cyclobutyl)-phenyl]-6-fluoro-2-phenyl-chromen-4-one, (1-{4-[6-(4-methyl-piperazin-1-yl)-4-oxo-2-phenyl-4H-chromen-3-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester was reacted to give the title compound as a yellow solid (12 mg, 96%). 1H NMR (400 MHz, DMSO-d6): as 7.63-7.56 (m, 2H), 7.41-7.29 (m, 8H), 7.13-7.09 (m, 2H), 3.25-3.20 (m, 4H), 2.52-2.47 (m, 4H), 2.41-2.32 (m, 2H), 2.24 (s, 3H), 2.12-2.04 (m, 2H), 2.04-1.94 (m, 1H), 1.69-1.60 (m, 1H). LCMS (Method F): RT=6.39 min, [M+H]+=466.
Reaction SMILES: [CH3:1][C@@H:2]([CH2:17][CH3:18])[C@H:3]([N:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16])[C:4]([O:6]C(C)(C)C)=[O:5].Cl>O1CCCC1>[CH3:1][C@@H:2]([CH2:17][CH3:18])[C@H:3]([N:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16])[C:4]([OH:6])=[O:5]
Reactant: CC[C@H](C)[C@@H](C(=O)OC(C)(C)C)N1CCNC1=O
Agent: Cl
Solvent: C1CCOC1
Product: CC[C@H](C)[C@@H](C(=O)O)N1CCNC1=O
Temperature: 60 °C
Reaction time: 12 h

Procedure:
To a solution containing the product from Example 161A (0.49 g, 1.91 mmol) in tetrahydrofuran (10.0 mL) was added aqueous HCl solution (5.0 mL, 4 N), and the mixture was stirred at 60° C. for 12 hours. The solvent was evaporated to give a white solid, which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](C)=[CH:15][CH2:16][OH:17])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.CN(C1C=CC2N=C3C(=CC(C=C3)=[N+](C)C)SC=2C=1)C.[C:39]1(=[O:44])[CH2:43][CH2:42][CH2:41][CH2:40]1.[O:45]1[CH2:50]CCOO1>CC#N.Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]([CH:14]=[CH:15][CH:16]3[CH2:50][O:45][C:39]4([CH2:43][CH2:42][CH2:41][CH2:40]4)[O:44][O:17]3)=[CH:12][CH:13]=2)=[CH:6][CH:7]=1
Reactant: O=C1CCCC1
Reactant: CC(=CCO)c1ccc(-c2ccc(Cl)cc2)cc1
Reactant: C1COOOC1
Agent: CN(C)c1ccc2nc3ccc(=[N+](C)C)cc-3sc2c1
Agent: Cl
Solvent: CC#N
Product: Clc1ccc(-c2ccc(C=CC3COC4(CCCC4)OO3)cc2)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 33.8 %

Procedure:
A solution of 3-(4′-chloro-[1,1′-biphenyl]4yl)-2-butenol (4g, 500 gm) and methylene blue (40 mg) in CH3CN (30 ml) was photooxygenated at 5° C. for 5 h. Cyclopentanone (0.5 ml) and hydrochloric acid (5 drops) were added and reaction mixture was stirred at r.t. for 1.5 h and then left at r.t for 48 h. The reaction mixture was concentrated. Crude product was purified by column chromatography to furnish 230 mg (33.8% yield, based on allylic alcohol, 4g used) of trioxane 7ga m.p. 105-107° C.
Reaction SMILES: [OH:1][C:2]1[C:19]2[C@@H:18]3[C@@H:9]([C@H:10]4[C@@:14]([CH2:16][CH2:17]3)([CH3:15])[C:13](=[O:20])[CH2:12][CH2:11]4)[CH2:8][CH2:7][C:6]=2[CH:5]=[C:4]([OH:21])[CH:3]=1.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>N1C=CC=CC=1>[S:23]([O:1][C:2]1[C:19]2[C@@H:18]3[C@@H:9]([C@H:10]4[C@@:14]([CH2:16][CH2:17]3)([CH3:15])[C:13](=[O:20])[CH2:12][CH2:11]4)[CH2:8][CH2:7][C:6]=2[CH:5]=[C:4]([O:21][S:23]([CH3:22])(=[O:25])=[O:24])[CH:3]=1)([CH3:22])(=[O:25])=[O:24]
Reactant: C[C@]12CC[C@@H]3c4c(O)cc(O)cc4CC[C@@H]3[C@@H]1CCC2=O
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: C[C@]12CC[C@@H]3c4c(cc(OS(C)(=O)=O)cc4OS(C)(=O)=O)CC[C@@H]3[C@@H]1CCC2=O
Temperature: 0 °C

Procedure:
A solution of 1 g. of 1,3-dihydroxy-8α-estra-1,3,5(10)-trien-17-one (prepared from compound of Example 9 by saponification) in 14 ml. of pyridine is combined at 0° C. with 1.9 ml. of methanesulfonic acid chloride and agitated for 3 days at 0°-10° C. The mixture is then introduced into ice water (acidified with HCl), filtered off, and the residue dissolved in methylene chloride. After chromatography on SiO2, 800 mg. of 1,3-bis(mesyloxy)-8α-estra-1,3,5(10)-trien-17-one is obtained.
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[NH3:6]>O>[C:1]([O-:5])(=[O:4])[CH:2]=[CH2:3].[NH4+:6].[C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3]
Reactant: N
Agent: C=CC(=O)O
Solvent: O
Product: C=CC(=O)[O-]
Product: [NH4+]

Procedure:
In 52.96 g of water, was dissolved 28.32 g of a reagent acrylic acid (guaranteed reagent grade manufactured by Wako Pure Chemical Industries, Ltd.). The resulting solution was cooled in an ice bath and slowly mixed with 18.35 g of a 25% by weight aqueous ammonia solution under stirring while keeping the mixture at a temperature of 30° C. or lower to obtain a 40% by weight aqueous ammonium acrylate/acrylic acid=70/30 solution. The aqueous ammonium acrylate/acrylic acid=70/30 solution in an amount of 90 g was brought to 10° C. and purged with nitrogen for 30 minutes, followed by addition of 0.72 g of ammonium carbonate and 0.147 g of triallylamine. To the resulting solution, were added as an initiator 0.1387 g of ammonium persulfate, 0.0322 g of a 30% by weight aqueous hydrogen peroxide solution, and 0.0016 g of L-ascorbic acid. Polymerization was performed for one hour to obtain a polymer, which was then crushed and dried at 150° C. for one hours in an inert oven with a nitrogen atmosphere. After drying, the polymer was further dried at 170° C. for 30 minutes in an inert oven with a nitrogen atmosphere. The resin obtained as described above was named as a comparative water-absorbing resin (3). The results of measurement of water absorption of the comparative water-absorbing resin (3) are shown in Table 2.
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].[C:11](F)(=[O:13])[CH3:12]>CC(O)=O>[CH3:3][CH:2]([CH2:1][C:5]1[CH:10]=[CH:9][C:8]([C:11]([CH3:12])=[O:13])=[CH:7][CH:6]=1)[CH3:4]
Reactant: CC(=O)F
Reactant: CC(C)Cc1ccccc1
Solvent: CC(=O)O
Product: CC(=O)c1ccc(CC(C)C)cc1

Procedure:
Isobutylbenzene (IBB) (10.2 lb/hr) and a solution of HF containing 13 wt % HOAc and 12 wt % acetyl fluoride (AcF) (153 lb/hr) were fed into reactor 1 through line 4. The mixture was reacted at 60° C. for 1.5 hrs to produce the desired 4-isobutylacetophenone product.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[C:12]1([CH:18]2[O:20][CH:19]2[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[H-].[Na+]>C(O)C.C(Cl)(Cl)Cl>[OH:20][CH:19]([CH:18]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[N+:9]([O-:11])=[O:10])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[C:21]([O:23][CH2:24][CH3:25])=[O:22]
Reactant: O=[N+]([O-])c1cc(Cl)ccc1O
Reactant: CCOC(=O)C1OC1c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CCO
Product: CCOC(=O)C(O)C(Oc1ccc(Cl)cc1[N+](=O)[O-])c1ccccc1
Yield: 32.6 %

Procedure:
To a stirred mixture of 4-chloro-2-nitrophenol (11.68 g, 67.32 mmol), ethyl 3-phenyloxirane-2-carboxylate (9.61 g, 50.00 mmol) in ethanol (200 mL) was added portionwise 60% sodium hydride (738 mg, 20.00 mmol) and the red mixture stirred at reflux for 3 days. The solvent was removed in vacuo. The residue was dissolved in chloroform and extracted three times with 10% aqueous potassium carbonate. The organic layer was washed with water and brine, dried, filtered and evaporated to afford a brown residue. The residue was dissolved in a minimal volume of chloroform and precipitated by adding diethyl ether to afford the title compound (5.970 g,33%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ1.16 (t, 3H, J=7.0 Hz), 4.09 (q, 2H, J=7.0 Hz), 4.29 (t, 1H, J=7.0 Hz), 5.63 (d, 1H, J=7.0 Hz), 6.09 (d, 1H, J=7.0 Hz), 7.19-7.60 (m, 7H), 7.97 (d, 1H, J=2.6 Hz). MS APCI, m/z=388 (M+Na).
Reaction SMILES: C(OC([NH:8][C@H:9]1[CH2:14][C@@H:13]([CH3:15])[CH2:12][N:11]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2[NH:22][C:23]([C:25]2[C:34]([NH:35][C:36](=[O:45])[O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[CH:33][C:32]3[C:27](=[CH:28][C:29]([N:46]4[CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)=[CH:30][CH:31]=3)[N:26]=2)=[O:24])[CH2:10]1)=O)(C)(C)C.[ClH:52]>O1CCOCC1.CO>[NH2:8][C@H:9]1[CH2:14][C@@H:13]([CH3:15])[CH2:12][N:11]([C:16]2[CH:21]=[CH:20][N:19]=[CH:18][C:17]=2[NH:22][C:23]([C:25]2[C:34]([NH:35][C:36](=[O:45])[O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[CH:33][C:32]3[C:27](=[CH:28][C:29]([N:46]4[CH2:47][CH2:48][O:49][CH2:50][CH2:51]4)=[CH:30][CH:31]=3)[N:26]=2)=[O:24])[CH2:10]1.[ClH:52]
Reactant: C[C@@H]1C[C@H](NC(=O)OC(C)(C)C)CN(c2ccncc2NC(=O)c2nc3cc(N4CCOCC4)ccc3cc2NC(=O)OCc2ccccc2)C1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: C[C@@H]1C[C@H](N)CN(c2ccncc2NC(=O)c2nc3cc(N4CCOCC4)ccc3cc2NC(=O)OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To the amide intermediate, 1 mL of 4 M HCl in dioxane and 1 mL of MeOH were added. The mixture was stirred at room temperature for 1 h, then concentrated under reduced pressure to give the sub-title compound as a HCl salt. LCMS calc. for C33H38N7O4 [M+H]+: m/z=596.3. found: 596.3.
Reaction SMILES: [Br:1][CH2:2][C:3]([C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([OH:14])=[C:7]([OH:15])[CH:6]=1)=O.[N:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[C:18]([NH:26][C:27]([NH2:29])=[S:28])[CH:17]=1>C(O)CCC>[BrH:1].[N+:11]([C:9]1[CH:10]=[C:5]([C:3]2[N:29]=[C:27]([NH:26][C:18]3[CH:17]=[N:16][C:25]4[C:20]([CH:19]=3)=[CH:21][CH:22]=[CH:23][CH:24]=4)[S:28][CH:2]=2)[CH:6]=[C:7]([OH:15])[C:8]=1[OH:14])([O-:13])=[O:12]
Reactant: NC(=S)Nc1cnc2ccccc2c1
Reactant: O=C(CBr)c1cc(O)c(O)c([N+](=O)[O-])c1
Solvent: CCCCO
Product: Br
Product: O=[N+]([O-])c1cc(-c2csc(Nc3cnc4ccccc4c3)n2)cc(O)c1O
Temperature: 25 °C

Procedure:
A suspension of 6.35 g of 2-bromo-3',4'-dihydroxy-5'-nitroacetophenone is treated with 4.68 g of 1-(3-quinolinyl)-2-thiourea in 150 ml of n-butanol and heated to boiling under reflux for 3 hours. After cooling to room temperature the crystals are filtered under suction and recrystallized from n-butanol. There is obtained 3-nitro-5-[2-(3-quinolinylamino)-4-thiazolyl]pyrocatechol hydrobromide of m.p.>300° .