Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH2:13][CH2:12]1.O.NN>[Pd].C(O)C>[F:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)[CH2:13][CH2:12]1)[NH2:8]
Reactant: COc1ccc(N2CCN(c3ccc([N+](=O)[O-])cc3F)CC2)cc1
Agent: [Pd]
Agent: NN
Solvent: CCO
Solvent: O
Product: COc1ccc(N2CCN(c3ccc(N)cc3F)CC2)cc1
Temperature: 25 °C
Yield: 94 %

Procedure:
To a stirred suspension of compound 3 (0.2 g, 0.6 mmol) and palladium catalyst (10% Pd on carbon 0.04 g) in ethanol (6 mL), hydrazine monohydrate (0.29 mL, 5.7 mmol) was added slowly and the reaction mixture was heated to reflux for 4 h. After cooling to room temperature, the reaction mixture was filtered and the filtrate was concentrated to obtain amine 4 (0.17 g, 93%).
Reaction SMILES: Cl.[CH3:2][O:3][N:4]1[CH2:10][CH2:9][NH:8][NH:7][CH2:6][CH2:5]1.C(N(CC)CC)C.C([O:20][C:21](=O)[CH:22]([C:28]1[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=1[CH3:36])[C:23](OCC)=[O:24])C.[OH-].[Na+]>C1(C)C(C)=CC=CC=1>[CH3:2][O:3][N:4]1[CH2:10][CH2:9][N:8]2[C:21](=[O:20])[CH:22]([C:28]3[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=3[CH3:36])[C:23](=[O:24])[N:7]2[CH2:6][CH2:5]1
Reactant: CON1CCNNCC1
Reactant: CCOC(=O)C(C(=O)OCC)c1c(C)cc(C)cc1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1C
Solvent: CCN(CC)CC
Product: CON1CCN2C(=O)C(c3c(C)cc(C)cc3C)C(=O)N2CC1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A degassed suspension of 5-methoxy-[1,2,5]triazepane hydrochloride salt (350 mg, 1.71 mmol) and triethylamine (1.0 ml, 726 mg, 7.17 mmol) in xylene (8 ml) was stirred under argon at 60° C. for one hour. After further addition of 2-(2,4,6-trimethyl-phenyl)-malonic acid diethyl ester (482 mg, 1.73 mmol), the reaction mixture was heated at 150° C. (oil bath temperature) for 18 hours. The cooled reaction mixture was poured on ice, the pH made alkaline by addition of 5N aqueous sodium hydroxide, the aqueous layer extracted twice with ethyl acetate and the combined organic layers discarded. The aqueous alkaline phase was acidified with cooling to pH 2-3 by addition of a 4N HCl solution and the product thoroughly extracted with dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The base-acidification workup protocol is repeated a second time. Yield: 24 mg of 3-methoxy-8-(2,4,6-trimethyl-phenyl)-tetrahydro-pyrazolo[1,2-a][1,2,5]triazepine-7,9-dione (compound P2.1) as a beige solid.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH:11]=O)([O-:3])=[O:2].[O:13]([C:15]([CH:17]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:16])[CH3:14]>C1(C)C=CC=CC=1>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1/[CH:10]=[CH:11]/[CH2:17][C:15]([O:13][CH3:14])=[O:16])([O-:3])=[O:2].[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10]/[CH:11]=[CH:17]/[C:15]([O:13][CH3:14])=[O:16])([O-:3])=[O:2]
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=CCc1ccccc1[N+](=O)[O-]
Solvent: Cc1ccccc1
Product: COC(=O)/C=C/Cc1ccccc1[N+](=O)[O-]
Product: COC(=O)C/C=C/c1ccccc1[N+](=O)[O-]
Temperature: 110 °C

Procedure:
A mixture of 2-(2-nitrophenyl)acetaldehyde (760 mg, 4.6 mmol) and methoxylcarbonylmethylenetriphenylphosphorane (1.5 g, 4.6 mmol) in toluene (10 mL) was heated at 110° C. for 3 hours. The crude material was purified by silica gel column chromatography eluting with hexanes and ethyl acetate (2:1) to afford the title compound along with (E)-methyl 4-(2-nitrophenyl)but-2-enoate.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH:16](O)[CH3:17])=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:13])([CH3:12])[C:10]=2[CH:11]=1.P(Br)(Br)[Br:20].O.[C:24]1([P:30]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CCOCC.CCCCCC>[Br-:20].[Cl:1][C:2]1[C:3]([CH:16]([P+:30]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH3:17])=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:13])([CH3:12])[C:10]=2[CH:11]=1
Reactant: CC(O)c1cc2c(cc1Cl)C(C)(C)CCC2(C)C
Reactant: BrP(Br)Br
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CCCCCC
Solvent: CCOCC
Product: CC(c1cc2c(cc1Cl)C(C)(C)CCC2(C)C)[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [Br-]
Reaction time: 1.5 h

Procedure:
To a solution of 3.15 g (11.8 mmol) of (±)-1-(3-chloro-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl) ethanol in ether and hexane stirring at 0° C. under argon, was added dropwise 31.9 g (11.2 mL, 118 mmol) of phosphorus tribromide and the mixture stirred 1.5 hours. Water was then carefully added and the mixture extracted with several portions of ether. The ether extracts were washed with water, sodium bicarbonate, brine, and dried (MgSO4). The solvent was removed in-vacuo and the residual oil taken up in 175 mL of benzene. To this was added 3.09 g (11.8 mmol) of triphenylphosphine and the solution stirred for 24 hours at room temperature. Purification was done using flash chromatography (SiO2, 0.5% ethyl acetate in hexanes, 5% MeOH in methylene chloride) to give the title compound as a white foam.
Reaction SMILES: [NH2:1][S:2]([C:5]1[S:6][C:7]([Cl:32])=[CH:8][C:9]=1[NH:10][C:11]([C:13]1[C:14](=[O:31])[N:15]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:16]2[C:21]([C:22]=1[OH:23])=[CH:20][CH:19]=[CH:18][CH:17]=2)=O)(=[O:4])=[O:3].NS(C1C=C(Br)C=CC=1NC(C1C(=O)N(CC2C=CC=CC=2)C2C(C=1O)=CC=CN=2)=O)(=O)=O>>[CH2:24]([N:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:22]([OH:23])=[C:13]([C:11]2[NH:10][C:9]3[CH:8]=[C:7]([Cl:32])[S:6][C:5]=3[S:2](=[O:4])(=[O:3])[N:1]=2)[C:14]1=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: NS(=O)(=O)c1sc(Cl)cc1NC(=O)c1c(O)c2ccccc2n(Cc2ccccc2)c1=O
Agent: NS(=O)(=O)c1cc(Br)ccc1NC(=O)c1c(O)c2cccnc2n(Cc2ccccc2)c1=O
Product: O=c1c(C2=NS(=O)(=O)c3sc(Cl)cc3N2)c(O)c2ccccc2n1Cc1ccccc1

Procedure:
The title compound is prepared according to the procedure of Example 84D substituting the product of Example 175A for the product of Example 84C.
Reaction SMILES: [OH-].[Na+].C1COCC1.[Cl:8][C:9]1[C:10]([CH2:35][NH:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=3)=[C:39]([CH3:50])[CH:38]=2)=[C:11]([C:19]2[CH:20]=[CH:21][C:22]([C:25]([NH:27][CH2:28][CH2:29][C:30]([O:32]CC)=[O:31])=[O:26])=[N:23][CH:24]=2)[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1.Cl>C(OCC)C.CO>[Cl:8][C:9]1[C:10]([CH2:35][NH:36][C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:44]=[CH:45][C:46]([Cl:49])=[CH:47][CH:48]=3)=[C:39]([CH3:50])[CH:38]=2)=[C:11]([C:19]2[CH:20]=[CH:21][C:22]([C:25]([NH:27][CH2:28][CH2:29][C:30]([OH:32])=[O:31])=[O:26])=[N:23][CH:24]=2)[CH:12]=[C:13]([C:15]([F:18])([F:16])[F:17])[CH:14]=1
Reactant: CCOC(=O)CCNC(=O)c1ccc(-c2cc(C(F)(F)F)cc(Cl)c2CNc2ccc(-c3ccc(Cl)cc3)c(C)c2)cn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: CO
Solvent: C1CCOC1
Product: Cc1cc(NCc2c(Cl)cc(C(F)(F)F)cc2-c2ccc(C(=O)NCCC(=O)O)nc2)ccc1-c1ccc(Cl)cc1
Temperature: 25 °C

Procedure:
A 3M aqueous solution of NaOH (1.9 mL, 5.7 mmol) was added to a THF (7.6 mL) and MeOH (3.8 mL) solution of ethyl 3-(5-(3-chloro-2-(((4′-chloro-2-methyl-[1,1′-biphenyl]-4-yl)amino)methyl)-5-(trifluoromethyl)phenyl)picolinamido)propanoate (2.4 g, 3.8 mmol) and the resulting homogeneous mixture was stirred at room temperature. After 30 min the resulting mixture concentrated and then acidified with 1M aqueous HCl. The resulting mixture was diluted with EtOAc and the layers were separated. The aqueous phase was extracted with EtOAc and the combined organics were washed with 4M NaCl, dried (Na2SO4), and concentrated. The resulting material was dissolved in diethyl ether, 1M diethyl ether solution of HCl (5.7 mL, 5.7 mmol) was added and the resulting precipitate was filtered, washed with diethyl ether, and dried in vacuo to yield the title compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([CH2:21][O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[CH2:29][C:30]([O:32]C)=[O:31])=[C:10]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13]([CH3:19])([CH3:18])[CH:12]=[C:11]3[CH3:20])=[C:4]([O:34][CH3:35])[CH:3]=1.C(OCC)(=O)C>CO.O1CCCC1.[OH-].[Na+]>[C:30]([CH2:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[O:22][CH2:21][C:9]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=2[O:34][CH3:35])=[CH:17][CH:16]=[C:15]2[C:10]=1[C:11]([CH3:20])=[CH:12][C:13]([CH3:18])([CH3:19])[NH:14]2)([OH:32])=[O:31]
Reactant: COC(=O)Cc1ccccc1OCc1c(-c2ccc(F)cc2OC)ccc2c1C(C)=CC(C)(C)N2
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: CCOC(C)=O
Product: COc1cc(F)ccc1-c1ccc2c(c1COc1ccccc1CC(=O)O)C(C)=CC(C)(C)N2
Temperature: 25 °C
Reaction time: 8 h
Yield: 89 %

Procedure:
6-(4-Fluoro-2-methoxyphenyl)-5-(2-methoxycarbonylmethylphenoxymethyl)-2,2,4-trimethyl-1,2-dihydroquinoline (Compound No. 14-1, 84.0 mg, 0.18 mmol) was dissolved in methanol (2 mL)—tetrahydrofuran mL) and 1N aqueous NaOH solution (0.56 mL) was added thereto and the mixture was stirred at room temperature overnight. After ethyl acetate (100 mL) was added to the reaction mixture, the whole was washed with 0.01N aqueous HCl solution (100 mL) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled compound (74.1 mg) as a colorless solid. (Yield 89%)
Reaction SMILES: Br[CH2:2][C:3]([CH3:16])=[CH:4][CH2:5][O:6][C:7]1[CH:15]=[CH:14][C:10]2[O:11][CH2:12][O:13][C:9]=2[CH:8]=1.[Na].[CH2:18]([S:22][O-])[CH:19]([CH3:21])[CH3:20]>C1C=CC=CC=1>[CH2:18]([S:22][CH2:2][C:3]([CH3:16])=[CH:4][CH2:5][O:6][C:7]1[CH:15]=[CH:14][C:10]2[O:11][CH2:12][O:13][C:9]=2[CH:8]=1)[CH:19]([CH3:21])[CH3:20]
Reactant: CC(=CCOc1ccc2c(c1)OCO2)CBr
Reactant: CC(C)CS[O-]
Agent: [Na]
Solvent: c1ccccc1
Product: CC(=CCOc1ccc2c(c1)OCO2)CSCC(C)C

Procedure:
A solution of 4.3 g (0.015 mol) of 5-(4-bromo-3-methyl-2-butenyloxy)-1,3-benzodioxol in 50 cc of benzene is added at 25° to 1.7 g (0.015 mol) of sodium-isobutylthio alcoholate in 30 cc of benzene The mixture is kept at reflux temperature for 13 hours, is subsequently filtered, washed with saturated salt solution and evaporated. The remaining yellow oil is chromatographed with hexane/ethyl acetate 7 : 1 on silica gel, whereby colourless 5-(4-isobutylthio-3-methyl-2-butenyloxy)-1,3-benzodioxol is obtained. nD20 = 1.5463.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C[C:15]1[CH:16]=[C:17]([N:22]2CC[NH:25][CH2:24][CH2:23]2)[CH:18]=[CH:19][C:20]=1[CH3:21]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:21][C:20]3[CH:19]=[C:18]4[C:17](=[CH:16][CH:15]=3)[NH:22][CH2:23][CH2:24][NH:25]4)[CH2:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: Fc1ccc(N2CCNCC2)cc1
Reactant: Cc1ccc(N2CCNCC2)cc1C
Product: Fc1ccc(N2CCN(Cc3ccc4c(c3)NCCN4)CC2)cc1

Procedure:
Example 6 was prepared according to Example 2 except that in Step A 1-(4-fluorophenyl)piperazine is substituted for 1-(3,4-dimethylphenyl)piperazine; mp 126°-127° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[C:9]([C:13]2[O:14][C:15]3[C:21]([C:22]([O:24]C)=O)=[CH:20][CH:19]=[CH:18][C:16]=3[N:17]=2)[CH:10]=[CH:11][CH:12]=1.[NH3:26]>CO>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[C:9]([C:13]2[O:14][C:15]3[C:21]([C:22]([NH2:26])=[O:24])=[CH:20][CH:19]=[CH:18][C:16]=3[N:17]=2)[CH:10]=[CH:11][CH:12]=1
Reactant: COC(=O)c1cccc2nc(-c3cccc(-c4ccccn4)c3)oc12
Reactant: N
Solvent: CO
Product: NC(=O)c1cccc2nc(-c3cccc(-c4ccccn4)c3)oc12
Temperature: 25 °C
Reaction time: 72 h
Yield: 74 %

Procedure:
Methyl 2-(3-(pyridin-2-yl)phenyl)benzo[d]oxazole-7-carboxylate (150 mg, 0.43 mmol) was added to ammonia in methanol (30 mL) and the mixture was stirred at room temperature for 3 days. Then the solid was filtered, washed with methanol, dried in vacuum. 100 mg of 2-(3-(pyridin-2-yl)phenyl)benzo[d]oxazole-7-carboxamide was obtained, yield: 74%. 1H-NMR (400 MHz, DMSO-d6) δ 7.44-7.47 (t, J=5.2 Hz, 1H), 7.50-7.54 (t, J=8.0 Hz, 1H), 7.76-7.88 (m, 3H), 7.96-8.01 (m, 3H), 8.12-8.14 (d, J=7.6 Hz, 1H); 8.35-8.39 (t, J=8.0 Hz, 2H); 8.76-8.77 (d, J=2.8 Hz, 1H); 9.01 (s, 1H); LC-MS (ESI) m/z: 316 (M+1)+.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[CH:12][CH:11]=[CH:10]2)(=O)=O.C(N(C(C)C)CC)(C)C.[CH3:28][Si:29]([CH3:50])([CH3:49])[CH2:30][CH2:31][O:32][CH2:33][N:34]1[CH:38]=[C:37]([C:39]2[CH:40]=[CH:41][C:42]3[N:43]([C:45]([SH:48])=[N:46][N:47]=3)[N:44]=2)[CH:36]=[N:35]1.C>CN(C=O)C>[CH3:28][Si:29]([CH3:50])([CH3:49])[CH2:30][CH2:31][O:32][CH2:33][N:34]1[CH:38]=[C:37]([C:39]2[CH:40]=[CH:41][C:42]3[N:43]([C:45]([S:48][C:7]4[CH:8]=[C:9]5[C:14](=[CH:15][CH:16]=4)[N:13]=[CH:12][CH:11]=[CH:10]5)=[N:46][N:47]=3)[N:44]=2)[CH:36]=[N:35]1
Reactant: C[Si](C)(C)CCOCn1cc(-c2ccc3nnc(S)n3n2)cn1
Reactant: O=S(=O)(Oc1ccc2ncccc2c1)C(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C[Si](C)(C)CCOCn1cc(-c2ccc3nnc(Sc4ccc5ncccc5c4)n3n2)cn1
Temperature: 70 °C
Yield: 37.1 %

Procedure:
A solution of 6-quinolinyl trifluoromethanesulfonate (436 mg, 1.57 mmol), diisopropylethylamine (0.746 mL, 4.29 mmol) in DMF (3.8 mL) under nitrogen was degassed by bubbling in nitrogen for 30 min. Tris(dibenzylideneacetone)dipalladium (33 mg, 2.5 mol %, Strem catalyst) and Xantphos (41 mg, 5 mol %) were added together in one portion, followed by 6-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (498 mg, 1.43 mmol) under a stream of nitrogen. The reaction mixture was stirred at 100° C. for 3 h before 500 mg of activated decolorizing charcoal were added. The suspension was stirred at 70° C. for 20, then the warm mixture was directly filtered through a plug of celite, using DMF as eluent. The solvent was evaporated in vacuo and the residue taken up in dichloromethane and washed with 1N aqueous NaOH and concentrated onto silica gel and purified by flash column chromatography eluting with dichloromethane:methanol 100:0 to 92:8 to return title compound as a light yellow foam (250 mg, 0.53 mmol, 37% yield): 1H NMR (DMSO-d6) δ 0.00 (9H, s), 0.90 (2H, t), 3.62 (2H, t), 5.54 (2H, s), 7.62 (1H, dd), 7.83 (1H, dd), 7.91 (1H, d), 8.07 (1H, d), 8.18 (1H, s), 8.23 (1H, d), 8.43 (1H, dd), 8.57 (1H, d), 8.75 (1H, d), 8.96 (1H, dd); MS (m/z) 476 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][C:10]#C)[CH:3]=1.[F-].[Cs+].[CH2:14](N(CC)C1C=CC=CC=1)C>C(OCC)(=O)C>[Br:1][C:2]1[C:3]2[CH:14]=[C:9]([CH3:10])[O:8][C:4]=2[CH:5]=[CH:6][CH:7]=1.[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[CH:14]=[C:9]([CH3:10])[O:8][C:4]=2[CH:3]=1
Reactant: CCN(CC)c1ccccc1
Reactant: C#CCOc1cccc(Br)c1
Agent: [Cs+]
Agent: [F-]
Solvent: CCOC(C)=O
Product: Cc1cc2c(Br)cccc2o1
Product: Cc1cc2ccc(Br)cc2o1
Temperature: 190 °C
Yield: 87 %
Yield: 13 %

Procedure:
To a solution of 49 (21 mmol) in N, N-diethylaniline (30 mL), cesium fluoride (11 mmol) was added and the mixture was heated at 190° C. for 24 h. After cooling, the suspension was diluted with ethyl acetate (100 mL) and washed with dil HCl (3×50 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated by rotary evaporation and purified column chromatography to give 4-bromo-2-methylbenzofuran (46g, 87%) and 6-bromo-2-methylbenzofuran (13%). The resulting mixture was purified by reverse phase HPLC using 10:1 acetonitrile: water with 0.1% TFA (B) for 22 min followed by 3 min at 100% B, to give compound 46g (26%).
Reaction SMILES: COP([C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10](=[O:17])NN=1)(=O)OC.[N+:18]([C:21]1[CH:22]=[C:23]([CH:26]=O)[S:24][CH:25]=1)([O-:20])=[O:19].C(N(CC)CC)C.C1C[O:38]CC1>O>[N+:18]([C:21]1[CH:22]=[C:23]([CH:26]=[C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:7](=[O:38])[O:17]2)[S:24][CH:25]=1)([O-:20])=[O:19]
Reactant: COP(=O)(OC)c1n[nH]c(=O)c2ccccc12
Reactant: O=Cc1cc([N+](=O)[O-])cs1
Reactant: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: O=C1OC(=Cc2cc([N+](=O)[O-])cs2)c2ccccc21
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of (4-oxo-3,4-dihydro-phthalazin-1-yl)-phosphonic acid dimethyl ester (3.85 g, 15.9 mmol) in THF (30 mL) was added 4-nitro-thiophene-2-carbaldehyde (25) (2.5 g, 15.9 mmol) under nitrogen. Triethylamine (2.2 mL 15.9 mmol) was added dropwise over 10 minutes and then stirred at room temperature for 4 hours. The yellow suspension was poured in water (80 mL), and the then filtered, the solid was washed with water (15 mL), hexane (10 mL) and then diethyl ether (10 mL) and then dried in vacuo to afford a 4.1 g of the desired products. Two peaks in LC-MS analysis, (4.1 g, 94%) and required no further purification; m/z (LC-MS, ESP), RT=4.71 mins (M+H) 274, & RT=4.84 mins (M+H) 274;
Reaction SMILES: CO[CH:3]([O:11]C)[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.C(OCC)C.C([Li])CCC.[CH3:23][C:24]1[O:30][C:27]([CH:28]=[O:29])=[CH:26][CH:25]=1>C(OCC)(=O)C.O>[OH:29][CH:28]([C:27]1[O:30][C:24]([CH3:23])=[CH:25][CH:26]=1)[C:7]1[CH:6]=[CH:5][C:4]([CH:3]=[O:11])=[CH:9][CH:8]=1
Reactant: COC(OC)c1ccc(Br)cc1
Reactant: Cc1ccc(C=O)o1
Agent: [Li]CCCC
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: Cc1ccc(C(O)c2ccc(C=O)cc2)o1
Reaction time: 0.33 h
Yield: 12.3 %

Procedure:
To a mixture of 4-bromobenzaldehyde dimethyl acetal (2.0 mL, 12 mmol) and diethyl ether (30 mL) was added dropwise n-butyl lithium (1.6 M n-hexane solution, 9.0 mL, 14 mmol) at −78° C., which was stirred for 20 minutes at the same temperature. 5-Methylfurfural (1.3 mL, 13 mmol) was added dropwise into the reaction mixture at that temperature, and stirred for 50 minutes at 0° C. Water and ethyl acetate were added to extract the reaction mixture. The organic layer was washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:2) to obtain the title compound (320 mg, 12%).
Reaction SMILES: [Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[CH3:11][O:12][C:13](=[O:20])[CH2:14][C:15](=[O:19])[CH2:16][O:17][CH3:18]>N1C=CC=CC=1.C(O)(=O)CCCCC.C1C=CC=CC=1>[CH3:11][O:12][C:13](=[O:20])[C:14](=[CH:4][C:3]1[CH:6]=[CH:7][CH:8]=[C:9]([Cl:10])[C:2]=1[Cl:1])[C:15](=[O:19])[CH2:16][O:17][CH3:18]
Reactant: COCC(=O)CC(=O)OC
Reactant: O=Cc1cccc(Cl)c1Cl
Solvent: c1ccccc1
Solvent: CCCCCC(=O)O
Solvent: c1ccncc1
Product: COCC(=O)C(=Cc1cccc(Cl)c1Cl)C(=O)OC
Yield: 95.8 %

Procedure:
A solution containing 160 ml of anhydrous benzene, 5 g of 2,3-dichlorobenzaldehyde, 4.2 g of 4-methoxy-3-oxo-butanoic acid methyl ester, 16 drops of pyridine and 22 drops of hexanoic acid is heated under reflux for one hour, removing the water formed. The mixture is then washed with a saturated sodium bicarbonate solution and then with a 0.1N hydrochloric acid solution. The organic phase is taken and evaporated to dryness so as to obtain 8.3 g of an oil.
Reaction SMILES: [OH:1][C:2]([CH3:13])([CH3:12])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)=[O:4].[H-].[Na+].Br[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>CS(C)=O>[OH:1][C:2]([CH3:13])([CH3:12])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:7][CH:6]=1)=[O:4].[CH3:12][C:2]([O:1][CH2:12][CH2:2][CH2:3][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])([CH3:13])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:7][CH:6]=1)=[O:4]
Reactant: CCCCCCCCBr
Reactant: CC(C)(O)C(=O)c1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CCCCCCCCOc1ccc(C(=O)C(C)(C)O)cc1
Product: CCCCCCCCOc1ccc(C(=O)C(C)(C)OCCCCCCCC)cc1
Temperature: 37.5 °C
Reaction time: 0.25 h
Yield: 5 %
Yield: 85 %

Procedure:
A solution of 2-hydroxy-1-(4-hydroxyphenyl)-2-methyl-1-propanone (10 g, 55.5 mmol) in dimethyl sulfoxide (DMSO) (125 ml) is added in the course of 1 hour at room temperature (RT), under argon, to a suspension of NaH (2.66 g, 61 mmol, 1.1 eq; 55–60% in oil, washed with hexane) in DMSO (40 ml). The mixture is stirred for 15 minutes at RT and for 15 minutes at from 35 to 40° C. A solution of 1-bromooctane (11.79 g, 61 mmol) in DMSO (10 ml) is added in the course of 15 minutes and the mixture is heated at 190° C. for 18 hours. The solution is poured onto ice and the resulting mixture is extracted with tert-butyl methyl ether (TBME). The organic phases are dried with MgSO4. After filtration and removal of the solvent by evaporation, the compound is obtained in the form of an oil. Flash chromatography yields 2-hydroxy-2-methyl-1-(4-octyloxy-phenyl)-propan-1-one (13.9 g, 85%) in the form of a yellow oil and 2-methyl-2-octyloxy-1-(4-octyloxy-phenyl)-propan-1-one (1.1 g; 5%) in the form of a yellow oil.
Reaction SMILES: [OH-:1].[Na+:2].[F:3][C:4]([F:13])([S:9](F)(=[O:11])=[O:10])[C:5]([O:7]C)=[O:6].Cl>O>[F:3][C:4]([F:13])([S:9]([OH:1])(=[O:11])=[O:10])[C:5]([O-:7])=[O:6].[Na+:2]
Reactant: COC(=O)C(F)(F)S(=O)(=O)F
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: O=C([O-])C(F)(F)S(=O)(=O)O
Temperature: 100 °C

Procedure:
460 Parts of 30% aqueous sodium hydroxide solution was added dropwise into a mixture of 200 parts of methyl difluoro(fluorosulfonyl)acetate and 300 parts of ion-exchanged water in a ice bath. The added mixture was heated and refluxed at 100° C. for 2.5 hours. After cooling, the cooled mixture was neutralized with 175 parts of conc. hydrochloric acid and concentrated to obtain 328.19 parts of sodium difluorosulfoacetate (containing inorganic salt, purity: 62.8%).
Reaction SMILES: [CH2:1]([N:15]([CH3:17])[CH3:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].C(#N)C.[Br:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>>[Br-:21].[CH2:1]([N+:15]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])([CH3:17])[CH3:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCCN(C)C
Reactant: CCCCCCCCBr
Solvent: CC#N
Product: CCCCCCCCCCCCCC[N+](C)(C)CCCCCCCC
Product: [Br-]
Temperature: 80 °C
Reaction time: 4 h

Procedure:
The procedure is as described in Example 1, but the following are added successively to the flask with stirring: 145.3 g (0.60 mol) of N-tetradecyl-N,N-dimethylamine, 267.0 g (6.5 mol) of acetonitrile and 121.7 g (0.63 mol) of 1-bromooctane. The mixture is heated to 80° C. with stirring and kept at this temperature for 4 hours and then cooled to room temperature, and an amine conversion of 98% is determined in a sample of the contents of the flask by a residual amine determination. Working-up is carried out as described in Example 1. The N-tetradecyl-N-octyl-N,N-dimethylammonium bromide (4) thus obtained is used for the viscosity determinations described below. The following contents are determined analytically: