Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCN(C(C)C)C(C)C.Cl.Cl.[C:12]1([C:18]2[C:19]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[C:20]3[CH:26]=[N:25][NH:24][C:21]3=[N:22][CH:23]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:33]([O:37][C:38]([N:40]1[C:44]([CH3:46])([CH3:45])[CH2:43][CH2:42][C@H:41]1[C@H:47]([C:51]1[CH:56]=[CH:55][C:54]([Cl:57])=[CH:53][CH:52]=1)[C:48](O)=[O:49])=[O:39])([CH3:36])([CH3:35])[CH3:34].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[Cl:57][C:54]1[CH:53]=[CH:52][C:51]([C@@H:47]([C@H:41]2[N:40]([C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:39])[C:44]([CH3:46])([CH3:45])[CH2:43][CH2:42]2)[C:48](=[O:49])[N:30]2[CH2:29][CH2:28][N:27]([C:19]3[C:18]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)=[CH:23][N:22]=[C:21]4[NH:24][N:25]=[CH:26][C:20]=34)[CH2:32][CH2:31]2)=[CH:56][CH:55]=1
Reactant: CC(C)(C)OC(=O)N1[C@H]([C@@H](C(=O)O)c2ccc(Cl)cc2)CCC1(C)C
Reactant: c1ccc(-c2cnc3[nH]ncc3c2N2CCNCC2)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1[C@H]([C@@H](C(=O)N2CCN(c3c(-c4ccccc4)cnc4[nH]ncc34)CC2)c2ccc(Cl)cc2)CCC1(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
DIEA (0.0475 mL, 0.273 mmol) was added to a solution of 5-phenyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]pyridine dihydrochloride (0.030 g, 0.0681 mmol, See Example 1), (S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(4-chlorophenyl)acetic acid (0.0251 g, 0.0681 mmol, see Example D) and TBTU (0.0263 g, 0.0818 mmol) in DCM (1 mL) and stirred at room temperature for 16 hours. The mixture was directly loaded onto a silica column and purified by chromatography (hexane:ethyl acetate, 1:1) to give (S)-tert-butyl 5-((S)-1-(4-chlorophenyl)-2-oxo-2-(4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)ethyl)-2,2-dimethylpyrrolidine-1-carboxylate as a solid. The solid was dissolved in DCM (1 mL), and TFA (0.2 mL) was added. The mixture was stirred at room temperature for 1 hour and then concentrated to dryness. The resulting residue was dissolved in DCM (0.5 mL), and HCl in ether (1 mL, 2N) was added. The resulting solid was collected by filtration to give (S)-2-(4-chlorophenyl)-2-((S)-5,5-dimethylpyrrolidin-2-yl)-1-(4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazin-1-yl)ethanone (0.019, 46%). MS APCI (+) m/z 529.3 detected.
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:6][O:5][C:4](=[O:7])[N:3]1[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1.[Br:17][C:18]1[CH:19]=[C:20]([CH3:30])[C:21]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[N:22][CH:23]=1>>[Br:17][C:18]1[CH:19]=[C:20]([CH3:30])[C:21]([N:24]2[CH2:25][CH2:26][N:27]([C:12]([C:11]3[CH:10]=[CH:9][C:8]([N:3]4[C@H:2]([CH3:1])[CH2:6][O:5][C:4]4=[O:7])=[CH:16][CH:15]=3)=[O:14])[CH2:28][CH2:29]2)=[N:22][CH:23]=1
Reactant: C[C@@H]1COC(=O)N1c1ccc(C(=O)O)cc1
Reactant: Cc1cc(Br)cnc1N1CCNCC1
Product: Cc1cc(Br)cnc1N1CCN(C(=O)c2ccc(N3C(=O)OC[C@H]3C)cc2)CC1
Yield: 96.7 %

Procedure:
By reaction and treatment in the same manner as in Preparation Example 67 and using (R)-4-(4-methyl-2-oxooxazolidin-3-yl)benzoic acid (1.3 g) described in Preparation Example 37 and 1-(5-bromo-3-methylpyridin-2-yl)piperazine (1.5 g), (R)-3-{4-[4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-4-methyloxazolidin-2-one (2.6 g) was obtained.
Reaction SMILES: Cl.[Cl:2][CH2:3][C:4]1[N:5]([CH2:17][CH2:18][CH2:19][NH:20]C(=O)OC(C)(C)C)[C:6]2[C:15]3[N:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1>CO>[ClH:2].[Cl:2][CH2:3][C:4]1[N:5]([CH2:17][CH2:18][CH2:19][NH2:20])[C:6]2[C:15]3[N:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1
Reactant: CC(C)(C)OC(=O)NCCCn1c(CCl)nc2cnc3cccnc3c21
Agent: Cl
Solvent: CO
Product: NCCCn1c(CCl)nc2cnc3cccnc3c21
Temperature: 25 °C
Reaction time: 72 h
Yield: 183.8 %

Procedure:
Concentrated hydrochloric acid (15 mL) was added to a suspension of tert-butyl 3-[2-(chloromethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]propylcarbamate (8.0 g, 21.3 mmol) in methanol (90 mL). The resulting solution was allowed to stir at room temperature for 72 hours. A solid formed that was isolated by filtration, washed with a minimal amount of methanol, and dried under vacuum to afford 6.11 g of 3-[2-(chloromethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]propan-1-amine hydrochloride as a pale yellow solid.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:12]([CH2:34][CH:35]([CH3:37])[CH3:36])[C@H:13]1[CH2:18][C@@H:17]([C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:20])[CH2:16][N:15]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:14]1)=[O:11].CS(O[CH2:43][CH2:44][C:45]1[S:46][CH:47]=[CH:48][CH:49]=1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:36][CH:35]([CH3:37])[CH2:34][N:12]([C:10]([C:2]1[N:3]([CH2:43][CH2:44][C:45]2[S:46][CH:47]=[CH:48][CH:49]=2)[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=1)=[O:11])[C@H:13]1[CH2:18][C@@H:17]([C:19]([N:21]2[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)=[O:20])[CH2:16][N:15]([C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])[CH2:14]1
Reactant: CC(C)CN(C(=O)c1nc2ccccc2[nH]1)[C@H]1C[C@@H](C(=O)N2CCOCC2)CN(C(=O)OC(C)(C)C)C1
Reactant: CS(=O)(=O)OCCc1cccs1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)CN(C(=O)c1nc2ccccc2n1CCc1cccs1)[C@H]1C[C@@H](C(=O)N2CCOCC2)CN(C(=O)OC(C)(C)C)C1
Temperature: 65 °C
Reaction time: 0.5 h
Yield: 85.6 %

Procedure:
tert-Butyl (3S,5R)-3-{(1H-benzimidazol-2-ylcarbonyl)(2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (150 mg) was dissolved in dimethylformamide (10 ml), 2-(thiophen-2-yl)ethyl methanesulfonate (90 mg) and cesium carbonate (190 mg) were added and the mixture was stirred at 65° C. for 30 min. 2-Thiophen-2-ylethyl methanesulfonate (90 mg) was added, and the mixture was further stirred for 1 hr. The reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, and a fraction eluted with ethyl acetate-hexane (1:9)-ethyl acetate was concentrated under reduced pressure to give the object product (156 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C@H:14]([N:15]([CH3:28])[C:16]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][N:19]=3)=[O:17])[CH2:13][CH2:12][N:11]([C:29]([C:31]3[NH:32][C:33]4[C:34](=[O:40])[CH2:35][CH2:36][CH2:37][C:38]=4[CH:39]=3)=[O:30])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[H-].[Na+].[CH3:43]I.O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C@H:14]([N:15]([CH3:28])[C:16]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:26])([F:25])[F:27])=[CH:20][N:19]=3)=[O:17])[CH2:13][CH2:12][N:11]([C:29]([C:31]3[N:32]([CH3:43])[C:33]4[C:34](=[O:40])[CH2:35][CH2:36][CH2:37][C:38]=4[CH:39]=3)=[O:30])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CN(C(=O)c1ccc(C(F)(F)F)cn1)[C@@H]1CCN(C(=O)c2cc3c([nH]2)C(=O)CCC3)C[C@H]1c1ccc(Cl)c(Cl)c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CN(C(=O)c1ccc(C(F)(F)F)cn1)[C@@H]1CCN(C(=O)c2cc3c(n2C)C(=O)CCC3)C[C@H]1c1ccc(Cl)c(Cl)c1
Reaction time: 0.17 h
Yield: 33 %

Procedure:
To a solution of the compound (0.060 g) obtained in Example 642 in DMF (1 mL) was added sodium hydride (0.005 g) and the mixture was stirred for 10 min. Methyl iodide (0.020 mL) was added at 0° C. and the mixture was stirred at room temperature. To the reaction mixture was added water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 30→70% ethyl acetate/hexane) to give the title compound (0.020 g, 33%) as a white powder.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]([NH:6][CH:7]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].[Cl:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](Cl)=[O:27])=[CH:24][CH:23]=1>>[Cl:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([NH:2][CH2:3][C:4](=[O:5])[NH:6][CH:7]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:27])=[CH:24][CH:23]=1
Reactant: NCC(=O)NC(c1ccccc1)c1ccc(Cl)cc1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Agent: Cl
Product: O=C(CNC(=O)c1ccc(Cl)cc1)NC(c1ccccc1)c1ccc(Cl)cc1

Procedure:
Prepared in analogy to example 1.13 from rac-2-amino-N-[(4-chloro-phenyl)-phenyl-methyl]-acetamide hydrochloride (Example 3.1) and 4-chlorobenzoyl chloride.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].C(N(CC)CC)C.[NH2:22][C:23]([CH3:27])([CH3:26])[CH2:24][OH:25]>ClCCl>[CH3:26][C:23]([CH3:27])([NH:22][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13])[CH2:24][OH:25]
Reactant: O=[N+]([O-])c1cnc2ccccc2c1Cl
Reactant: CC(C)(N)CO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(CO)Nc1c([N+](=O)[O-])cnc2ccccc12
Temperature: 20 °C
Reaction time: 16 h

Procedure:
To a stirred solution of 67.1 g (0.322 mole) of 4-chloro-3-nitroquinoline in 800 mL of dichloromethane was added 54 mL (0.38 mole) of triethylamine and 96 mL (0.96 mole) of 2-amino-2-methyl-1-propanol. The mixture was heated at reflux for one hour, then stirred at about 20° C. for about 16 hours. The mixture was concentrated by evaporation in vacuo and the residue was slurred in 1.5 l of water. The product was separated by filtration and dried to provide solid 2,2-dimethyl-2-[(3-nitro-4-quinolinyl)amino]ethanol. The structural assignment was confirmed by comparison of the nuclear magnetic resonance spectrum to that of a sample which was previously used for elemental analysis. Analysis of earlier sample: Calculated for C13H15 N3O2 : % C, 59.8; % H, 5.8; % N, 16.1; Found % C, 59.9; % H, 5.8; % N, 16.1.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:23]=[C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:21]([C:32]([CH3:34])=[CH2:33])=[CH:20][C:10]=1[C:11]([N:13]([CH2:17][C:18]#[CH:19])[CH2:14][C:15]#[CH:16])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:35]([OH:39])[CH2:36][C:37]#[CH:38].CCCCCCC>C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:23]=[C:22]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:21]([C:32]([CH3:34])=[CH2:33])=[CH:20][C:10]=1[C:11]([N:13]1[CH2:17][C:18]2[C:15](=[CH:16][CH:38]=[C:37]([CH2:36][CH2:35][OH:39])[CH:19]=2)[CH2:14]1)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C#CCCO
Reactant: C#CCN(CC#C)C(=O)c1cc(C(=C)C)c(OCc2ccccc2)cc1OCc1ccccc1
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: C=C(C)c1cc(C(=O)N2Cc3ccc(CCO)cc3C2)c(OCc2ccccc2)cc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 40.7 %

Procedure:
To a solution of 2,4-bis-benzyloxy-5-isopropenyl-N,N-di-prop-2-ynyl-benzamide (0.940 g, 2.1 mmol) in ethyl acetate (2 mL) was added 3-butyn-1-ol (0.30 mL, 4.0 mmol) and RhCl(PPh3)3 (0.162 g, 0.17 mmol). The mixture was stirred at room temperature for 24 hours, then loaded directly onto a silica gel column, eluting with 7:3 ethyl acetate:heptane to give the desired product (0.444 g, 38% yield). LC/MS: m/z 520.25 [M+H]+
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][S:14]([OH:17])(=O)=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)(Cl)[Cl:19]>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][S:14]([Cl:19])(=[O:17])=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(NCCS(=O)(=O)O)OCc1ccccc1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Product: O=C(NCCS(=O)(=O)Cl)OCc1ccccc1
Temperature: 25 °C

Procedure:
2-(N-benzyloxycarbonylamino)ethanesulfonic acid (0.6 g; 2.31 mmol) was suspended in dry toluene (6 mL) and PCl5 was added (0.65 g; 3.11 mmol). The mixture was refluxed for 2 h, until complete dissolution of the reagents. After cooling at room temperature, the solvent was evaporated off under vacuum to give the crude 2-(N-benzyloxycarbonylamino)-ethanesulfonyl chloride pure enough for the next step.
Reaction SMILES: [H-].[K+].O1CCOCC1.[CH:9]([S:12][CH2:13][S:14](=[O:18])[CH:15]([CH3:17])[CH3:16])([CH3:11])[CH3:10].Br[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]Br>C(Cl)Cl>[CH:9]([S:12][C:13]1([S:14](=[O:18])[CH:15]([CH3:17])[CH3:16])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)([CH3:11])[CH3:10]
Reactant: CC(C)SCS(=O)C(C)C
Reactant: BrCCCCCBr
Agent: [H-]
Agent: [K+]
Solvent: ClCCl
Solvent: C1COCCO1
Product: CC(C)SC1(S(=O)C(C)C)CCCCC1
Reaction time: 1 h
Yield: 58.9 %

Procedure:
Potassium hydride (995 mg) was suspended in 15 ml. of dioxane, and with ice cooling, 1.804 g of formaldehyde diisopropyl mercaptal S-oxide was added gradually. The mixture was stirred for 1 hour with ice cooling, and then 2.411 g of 1,5-dibromopentane was added. Then, the mixture was stirred for 18 hours at room temperature. Methylene chloride (100ml) was added, and the isoluble matter was separated by filtration. After the evaporation of the filtrate at reduced pressure, the residue was separated by column chromatography (basic alumina, eluted with benzene, methylene chloride, and ethyl acetate) to afford 1.463 g of cyclohexanone diisopropyl mercaptal S-oxide as a colorless oil. The yield was 59%. The physical properties and the results of elemental analysis were as follows:
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH2:3][CH2:2]1.[CH3:8][O:9][C:10]1[CH:57]=[CH:56][C:13]([CH2:14][O:15][C@@H:16]2[C@@H:23]([CH2:24][OH:25])[O:22][C@H:19]([O:20][CH3:21])[C@H:18]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C@H:17]2[O:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])=[CH:12][CH:11]=1>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[C:4]([CH2:3][CH2:2][C:1]([O:25][CH2:24][C@H:23]1[O:22][C@H:19]([O:20][CH3:21])[C@H:18]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C@@H:17]([O:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH3:55])[C@@H:16]1[O:15][CH2:14][C:13]1[CH:12]=[CH:11][C:10]([O:9][CH3:8])=[CH:57][CH:56]=1)=[O:7])([OH:6])=[O:5]
Reactant: O=C1CCC(=O)O1
Reactant: CCCCCCCCCCCCCCO[C@@H]1[C@@H](OCCCCCCCCCCCCCC)[C@@H](OC)O[C@H](CO)[C@H]1OCc1ccc(OC)cc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCO[C@@H]1[C@@H](OCCCCCCCCCCCCCC)[C@@H](OC)O[C@H](COC(=O)CCC(=O)O)[C@H]1OCc1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 89.3 %

Procedure:
DMAP (7.0 mg, 0.05 mmol) and succinic anhydride (71 mg, 0.70 mmol) were added to a stirred solution of methyl 4-O-p-methoxybenzyl-2,3-di-O-tetradecanyl-α-D-glucopyranoside 21 (Price et al., Proc. Natl. Acad. Sci., USA, 1995, 92, 7352-7356) (0.40 g, 0.56 mmol) in dry pyridine (5 mL) and the resulting reaction mixture was stirred for 16 h at rt under argon. After that, the reaction mixture was concentrated under the reduced pressure. The residue was dissolved in CH2Cl2 (30 mL) and washed successively with 1N HCl (2×15 mL), water (2×15 mL) and brine (15 mL). The organic phase was separated, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (ethyl acetate-hexane gradient elution) to give the title compound 22 (0.41 g, 0.50 mmol) as a colorless syrup in 89% yield. Analytical data for 22: Rf=0.55 (ethyl acetate/hexane, 7/3, v/v); [α]D24+42.9° (c=1.0, CHCl3); 1H NMR (300 MHz, CDCl3): δ, 0.88 (t, 6H, 2×CH3), 1.26 (br. s, 40H, 22×CH2), 1.63 (m, 4H, 2×CH2), 2.64 (m, 2H, 2×CH2), 3.30 (dd, 1H, J2,3=9.7 Hz, H-2), 3.38 (s, 3H, OCH3), 3.39 (m, H-4), 3.59-3.76 (m, 5H, H-3, 5, OCH2, OCH2a), 3.80 (s, 3H, OCH3), 3.86 (m, 1H, OCH2b), 4.28 (m, 2H, J5,6b=4.7 Hz, J5,6a=2.3 Hz, J6a,6b=12.0 Hz, H-6a, 6b), 4.49 (d, 1H, J2=10.5 Hz, ½CH2Ph), 4.76 (d, 1H, J1,2=3.5 Hz, H-1), 4.81 (d, 1H, J2=10.5 Hz, ½CH2Ph), 6.89 (d, 2H, J=8.9 Hz, aromatic), 7.22 (d, 2H, J=9.7 Hz, aromatic) ppm; 13C NMR (125 MHz, CDCl3): δ=14.3, 22.9, 26.2, 26.5, 28.8, 28.9, 29.5, 29.7, 29.8, 29.9 (×2), 30.3, 30.8, 32.1, 55.3, 55.5, 63.6, 68.8, 72.0, 74.1, 74.8, 80.9, 81.9, 98.1, 114.1, 130.1, 130.4, 159.6, 172.0, 176.5 ppm; HR FAB MS [M+Na]+ calcd for C47H82O10Na 829.5805. found 829.5806.
Reaction SMILES: [Br:1]Br.[F:3][C:4]([F:15])([F:14])[C:5]1[CH:6]=[C:7]([C:11](=[O:13])[CH3:12])[CH:8]=[CH:9][CH:10]=1>C(OCC)C>[Br:1][CH2:12][C:11]([C:7]1[CH:8]=[CH:9][CH:10]=[C:5]([C:4]([F:14])([F:15])[F:3])[CH:6]=1)=[O:13]
Reactant: BrBr
Reactant: CC(=O)c1cccc(C(F)(F)F)c1
Solvent: CCOCC
Product: O=C(CBr)c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Bromine (4.25 g, 26.6 mmol) was slowly added dropwise to a solution of 1-[3-(trifluoromethyl)phenyl]ethanone (5.00 g, 26.6 mmol) in diethyl ether (100 ml), and the mixture was stirred at room temperature for 4 hours. The reaction mixture was distilled off under reduced pressure to give the desired product as an oil quantitatively.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([C:17]#[C:18][CH2:19][OH:20])=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:4][CH:3]=1.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([C:17]#[C:18][CH2:19][O:20][S:22]([CH3:21])(=[O:24])=[O:23])=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)Cl
Reactant: OCC#Cc1ccc2c(-c3ccc(Cl)cc3)nsc2c1
Product: CS(=O)(=O)OCC#Cc1ccc2c(-c3ccc(Cl)cc3)nsc2c1

Procedure:
In analogy to example 15.1, 3-[3-(4-Chloro-phenyl)-benzo[d]isothiazol-6-yl]-prop-2-yn-1-ol and methane sulfonyl chloride were converted to yield Methanesulfonic acid 3-[3-(4-chloro-phenyl)-benzo[d]isothiazol-6-yl]-prop-2-ynyl ester as a brown oil, MS: 377 (M, 1Cl).
Reaction SMILES: CO[CH:3]1[CH2:7][CH2:6][CH:5](OC)O1.Br.[NH:11]([C:13]1[NH:14][CH2:15][CH2:16][N:17]=1)[NH2:12].[OH-].[Na+]>>[N:12]1([NH:11][C:13]2[NH:17][CH2:16][CH2:15][N:14]=2)[CH:3]=[CH:7][CH:6]=[CH:5]1
Reactant: COC1CCC(OC)O1
Reactant: NNC1=NCCN1
Agent: Br
Agent: [Na+]
Agent: [OH-]
Product: c1ccn(NC2=NCCN2)c1

Procedure:
By reacting 3.7 g. (0.0280 mole) of 2,5-dimethoxy-tetrahydrofuran with 5 g. (0.0276 mole) of 2-hydrazino-4,5-dihydro-1H-imidazole hydrobromide according to the process reported in Example 3, and adding at the end of the reaction a 10% aqueous solution of sodium hydroxide, the title compound is obtained as the free base. Yield 1.5 g. M.p. 183°-4°C. (from acetone.) The maleate melts at 142°-5°C (from acetone).
Reaction SMILES: O[C:2]([CH3:12])([CH3:11])[C:3](C1C=CC=CC=1)=[O:4].O[CH2:14][CH:15]([CH2:17][OH:18])[OH:16]>>[C:3]([O:18][CH2:17][CH:15]1[O:16][CH2:14]1)(=[O:4])[C:2]([CH3:12])=[CH2:11]
Reactant: CC(C)(O)C(=O)c1ccccc1
Reactant: OCC(O)CO
Product: C=C(C)C(=O)OCC1CO1
Reaction time: 8 h

Procedure:
After sitting overnight a 50 g portion of each of the 15,000 and 10,000 mw functionalized materials were formulated with 49 g of glycerin and 1 g of 2-hydroxy-2-methyl-1-phenyl-propan-1-one, a photoinitiator available from Ciba-Giegy Corporation, Hawthorne, N.Y. under the tradename Darocur® 1173.
Reaction SMILES: [C:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5]1=[O:13])([CH3:3])=[CH2:2].[Br:14][CH2:15][CH2:16]Br.[H-].[Na+]>CN(C=O)C>[C:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([CH2:16][CH2:15][Br:14])[C:5]1=[O:13])([CH3:3])=[CH2:2]
Reactant: C=C(C)n1c(=O)[nH]c2ccccc21
Reactant: BrCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=C(C)n1c(=O)n(CCBr)c2ccccc21

Procedure:
1-Isopropenylbenzimidazolone (J. Davol, J. Chem. Soc., 1960, 308) was alkylated with 1,2-dibromoethane using sodium hydride in DMF. The product was purified by chromatography and crystallization from cyclohexane to give 1-isopropenyl-3-(2-bromoethyl)benzimidazolone.
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[O:17][C:16](=O)[NH:15][C:14](=[O:20])[C:13]=3[CH2:12][O:11][CH2:10]2)=[CH:5][CH:4]=1.[OH-].[NH4+:24]>>[F:1][C:2]([F:22])([F:21])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[NH:24][C:16](=[O:17])[NH:15][C:14](=[O:20])[C:13]=3[CH2:12][O:11][CH2:10]2)=[CH:5][CH:4]=1
Reactant: O=c1[nH]c(=O)c2c(o1)C(c1ccc(C(F)(F)F)cc1)COC2
Reactant: [NH4+]
Agent: [OH-]
Product: O=c1[nH]c2c(c(=O)[nH]1)COCC2c1ccc(C(F)(F)F)cc1

Procedure:
8-(4-(trifluoromethyl)phenyl)-7,8-dihydropyrano[3,4-e][1,3]oxazine-2,4(3H,5H)-dione (Intermediate Z(3)) was reacted as described in Intermediate X(4) with ammonium hydroxide to give 8-(4-(trifluoromethyl)phenyl)-7,8-dihydro-1H-pyrano[4,3-d]pyrimidine-2,4(3H,5H)-dione (Intermediate Z(4)). LC-MS (M−H)+=313.1.
Reaction SMILES: CS([C:5]1[N:10]=[C:9]([N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[CH:12]2)[CH:8]=[CH:7][N:6]=1)(=O)=O.[N+:20]([C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH2:26][NH2:27])([O-:22])=[O:21]>>[N+:20]([C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH2:26][NH:27][C:5]1[N:10]=[C:9]([N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[CH:12]2)[CH:8]=[CH:7][N:6]=1)([O-:22])=[O:21]
Reactant: CS(=O)(=O)c1nccc(-n2cnc3ccccc32)n1
Reactant: NCc1cccc([N+](=O)[O-])c1
Product: O=[N+]([O-])c1cccc(CNc2nccc(-n3cnc4ccccc43)n2)c1

Procedure:
2-Methanesulfonyl-4-[benzimidazol-1-yl]pyrimidine was reacted with 3-nitrobenzylamine according to the procedure described in EXAMPLE 1, Step C to afford the title compound. Mass Spectrum (ESI): m/e 347.0 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.58 (br s, 1H); 8.46 (d, J=5.5 Hz, 1H); 8.31 (s, 1H); 8.17 (d, J=8.5 Hz, 1H); 8.00 (br s, 1H); 7.85 (d, J=8.0 Hz, 1H); 7.77 (d, J=7.6 Hz, 1H); 7.56 (t, J=7.9 Hz, 1H); 7.38 (m, 2H); 6.90 (d, J=5.5 Hz, 1H); 5.94 (br s, 1H); 4.87 (d, J=6.2 Hz, 2H).
Reaction SMILES: [CH2:1]([C:13]1[CH:17]=[CH:16][S:15][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[Li+].CC([N-]C(C)C)C.[CH3:26][Sn:27](Cl)([CH3:29])[CH3:28]>C1COCC1>[CH3:26][Sn:27]([CH3:29])([CH3:28])[C:16]1[S:15][CH:14]=[C:13]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH:17]=1
Reactant: CCCCCCCCCCCCc1ccsc1
Reactant: C[Sn](C)(C)Cl
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCCCCCCCCCCc1csc([Sn](C)(C)C)c1
Temperature: -78 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
To a stirred degassed homogeneous solution of 3-dodecyl thiophene (19) (2 g, 7.92 mmol) in THF at −78° C. was added LDA (4.75 ml, 9.51 mmol) drop wise. The mixture was stirred at −78° C. for 1 h, then trimethylstannylchloride dissolved in 9.5 ml of THF was added, and the solution warmed to room temperature. Stirring was continued for 2 h at room temperature. The mixture was washed with saturated NaHCO3 and extracted with diethylether. The organic layer was separated and dried over anhydrous sodium sulphate and concentrated under reduced pressure to give desired product 20 in 90% yield. 1H-NMR (CD2Cl2, 400 MHz) δ 7.19 (s, 1H), 7.02 (s, 1H), 2.63 (t, 2H), 1.62 (m. 2H), 1.2-1.4 (m, 18H), 0.88 (t, 3H), 0.34 (s, 9H).